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European\tUnion’s\tHorizon\t2020\tresearch\tand\tinnovation\tprogram\tis\tdeveloping\tanother\tasset,\nthe\tELSI\tKnowledge\tDesk\twhich\tis\talso\tavailable\n\ton\ttheir\twebsite.\tDatabases\tare\talso\tavailable\nthat\tcan\tbe\thelpful\tto\tresearchers\tand\tconsumers,\tsuch\tas\tthe\tELSI\tHelpdesk\tand\tELSI
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five\tletters\tand\twritten\tin\titalics.\tFor\tthe\nvast\tnumber\tof\tgenes,\thuman\tbeings\thave\ttwo\tcopies.\tTherefore\twhen\tdescribing\tthe\tgene\tand\nnucleotides\tpresent\t(whether\twild-type/usual\tor\tvariant/mutant)\tcertain\tconventions\tare\tused.\tIf\tthe\ntwo\tnucleotides\tare\twild-type,\tthe\tindividual\tis\tdescribed\tas\tbeing\thomozygous\twild-type.\tIf\tone\twild-
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type\tand\tone\tvariant\tare\tpresent,\tthe\tindividual\tis\theterozygous,\n\talso\tcalled\ta\t“carrier.”\tIf\tboth\nnucleotides\tare\tthe\tvariant\tnucleotide,\tthe\tindividual\tis\thomozygous\tvariant.\tWild-type\tand\tvariant\nstates\tmay\tbe\treferred\tto\tas\tthe\twild-type\tallele\tand\tthe\tvariant\tor\trisk\tallele,\twhich\tsimply\trefers\tto
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replaced\tby\ta\tT\t(thymidine)\tnucleotide\tat\tposition\t677\tin\tthe\t\nMTHFR\n\tgene\tsequence.\tIndividuals\nhomozygous\twild-type\thave\ta\tC\tat\tthis\tposition\tin\tboth\tcopies\tof\tthis\tgene.\tHeterozygotes\thave\t1\tC\nand\t1\tT\tand\tthose\thomozygous\tfor\n\tthe\tvariant\thave\ta\tT\tat\tthis\tposition\tin\tboth\tcopies\tof\tthe\tgene.\nAdditionally,\teach\tvariant\tis\tassigned\tan\t“\nrs\tnumber
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Additionally,\teach\tvariant\tis\tassigned\tan\t“\nrs\tnumber\n”\t(reference\tSNP\tcluster\tID).\tThe\tabove\nMTHFR\n\tvariant\tis\trs1801133.\tA\tdifferent\tvariant\twithin\tthis\tsame\tgene\tis\tthe\t\nMTHFR\n\tA1298C\tand\tis\nlabeled\trs1801131).\tThe\trs\tnumber\tis\tcritical\tbecause\tit\tdenotes\ta\tspecific\tlocation\twithin\tthe\tDNA\nand\tdifferent\tmutations\toften\tcreate\tdifferent
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and\tdifferent\tmutations\toften\tcreate\tdifferent\n\tfunctional\toutcomes.\tThe\tlack\tof\trs\tnumbers\tin\tthe\nearlier\tgenomic\tliterature\thas\toften\tmade\tit\tdifficult\tto\tdiscern\twhich\tmutation\tis\tbeing\tanalyzed\tfor\nits\tgene-environment\tinteractions.\tBoth\tresearchers\tand\tcommercial\tcompanies\ttypically\tnow\tgive
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the\trs\tnumber\talong\twith\tthe\tvariant’s\tgene\tand\tmutation.\tSNPs,\tsuch\tas\t\nMTHFR,\n\tare\tthe\tmost\ncommon\ttype\tof\tmutation\tencountered\tin\tnutrigenetic\ttesting\n\tbut\tbe\taware\tthat\tother\ttypes\tof\nmutations\tare\tpossible,\tsuch\tas\tdeletions,\tinsertions,\tand\tcopy\tnumber\tvariants\tand\tthat\teach\nvariant\thas\tan\trs\tnumber.
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variant\thas\tan\trs\tnumber.\nThe\tnext\tstep\tis\tto\ttake\tthe\tvariants\tidentified\tand\tmake\tpredictions\tas\tto\twhich\tvariants\tincrease\none’s\tsusceptibility\tto\tparticular\tdiseases\tand\tthen\tto\tselect\tappropriate\thealth-promoting\ninterventions\tfor\tthese\tsusceptibilities.\tMany\tgenomics\n\tresearchers\tand\thealth\tcare\tprofessionals
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researchers\tand\thealth\tcare\tprofessionals\nquestion\tthe\treliability\tof\tthe\ttesting\tand\tits\tpresent\tclinical\tutility.\tThe\tweakness\twould\tseem\tnot\tto\nbe\tthe\ttechnology\titself,\twhich\thas\tbeen\tin\tplace\tfor\tdecades\tand\tis\ta\tmainstay\tin\tresearch\nlaboratories\tand,\tmore\trecently,\tin\tclinical\tlaboratories.\tThe\tweakness\tis\tthe\tlink\tbetween\ta
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interventions\tare\ttypically\tantiinflammatory\tin\tnature\tacross\tthe\tboard\tfor\teach\tof\tthe\tprimary\nlifestyle\trecommendations:\tnutrition,\tphysical\tactivity,\tmanaging\tthoughts\tand\temotions,\tdeveloping\nsupportive\trelationships,\tobtaining\tsufficient\tquantity\tand\tquality\tof\tsleep,\tand\tminimizing\ttoxin
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those\tassociated\twith\tinflammatory\tbiomarkers:\tC-reactive\tprotein\t(\nCRP\n),\tinterleukin-1beta\t(\nIL1ß\n),\ninterleukin-6\t(\nIL6\n),\tand\ttumor\tnecrosis\tfactor\talpha\t(\nTNF\n).\t\nCRP\n\tis\tproduced\tby\tthe\tliver\tin\tresponse\nto\tinflammation.\tInterleukin-1\tand\tinterleukin-6\tproteins\tare\tcytokines\tproduced\tas\tpart\tof\n\tthe
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the\ninflammatory\tprocess.\tThese\tproteins\tfunction\tas\tcell\tsignaling\tmolecules\tthat\tactivate\tthe\timmune\nsystem,\twhich\tinvolves\tinflammatory\tprocesses.\tInflammation\tis\ttypically\tself-limiting\tand\tabates\nwhen\tthe\tinfection\tor\tinjury\tis\tunder\tcontrol.\tIn\tthe\tcase\tof\tchronic\tdisease,\thowever,\tthe
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inflammatory\tresponse\tis\tessentially\tstuck\tin\tthe\t“on”\tposition.\nBiotransformation\t(detoxification)\nA\tparallel\tbetween\tpharmacogenomics\tand\tnutritional\tgenomics\tcan\tbe\tseen\twith\tthe\tphase\tI\tand\nphase\tII\tbiotransformation/detoxification\tpathways\tthat\tare\tactive\tin\tthe\tdigestive\ttract\tand\tliver.\tIn
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0.027288032695651054, -0.09680826216936111, 0.10218092799186707, 0.061786822974681854, -4.544985188204009e-8, 0.040451280772686005, -0.051808733493089676, 0.059620242565870285, -0.00793516170233488, -0.006070947740226984, -0.01718073897063732, 0.02816018834710121, 0.07972138375043869, -0.021593403071165085, -0.032456330955028534, 0.050545208156108856, 0.13979142904281616, -0.09279346466064453, -0.02789386361837387, 0.07025959342718124, 0.04186642915010452, -0.050413090735673904, 0.03057047724723816, -0.014284911565482616, -0.055769722908735275, -0.03566830977797508, 0.0649203509092331, -0.02211529202759266, 0.01092291995882988, 0.01796075329184532, -0.006412745453417301, 0.01136729121208191, 0.043150946497917175, 0.01960439793765545, 0.018144778907299042, 0.06588956713676453, -0.028560318052768707, -0.03661319240927696, -0.008437146432697773, -0.0743657723069191, 0.031452033668756485, 0.04423379525542259, -0.08054400980472565, -0.04611949622631073, 0.12578362226486206, -0.04425831884145737, -0.015333685092628002, -0.045848578214645386, 0.06259150058031082, 0.015225201845169067, -0.04592273011803627, -0.016333114355802536, 0.09736932069063187, 0.024019354954361916, -0.08559266477823257, 0.018259797245264053, 0.062081318348646164, -0.025841832160949707, 0.008143696002662182, -0.047995876520872116, 0.06433164328336716, 0.09837658703327179, 0.06052533537149429, 0.013237535953521729, -0.03214798495173454, 0.086139976978302, 0.0662304237484932, 0.12490673363208771, -0.051647696644067764 ]
a\ttwo-phase\tprocess,\tthis\tmetabolic\tsystem\tconverts\tdrugs\tand\tother\tpotentially\ttoxic\tmolecules\tinto\nchemical\tforms\tthat\tcan\tbe\texcreted.\tPhase\tI\tactivates\tthe\ttoxic\tmolecule\tto\tform\ta\treactive\toxygen\nspecies\t(free\tradical)\tthrough\tthe\tactivity\tof\tvarious\tcytochrome\tP450\tenzymes\t(CYPs).
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Subsequently,\tin\tPhase\tII\tglutathione-S-transferases\t(GSTs)\tand\tother\tenzymes\tadd\tchemical\tgroups\nto\tthe\tactivated\tmolecule\tto\trender\tit\tmore\tsoluble\tand\tless\ttoxic.\tKnowing\tthe\tgenomic\tstatus\tof\tthe\ngenes\tthat\tcode\tfor\tthese\tvarious\tenzymes\twould\tbe\thelpful\tfor\tpredicting\twhich\tnutritional\napproaches\twould\tbe\tbeneficial
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approaches\twould\tbe\tbeneficial\n\tto\tsupport\tthe\tbiotransformation\tprocess\tand\twhen\tspecific\nmedications\tare\tused\t(see\t\nBox\t6.14\n).\nThe\tgene\tvariants\tcommonly\tfound\tin\tgenetic\ttest\tpanels\tthat\tinclude\tbiotransformation\tare\tfrom\nthe\tfamily\tof\t\nCYP\n\tgenes,\tthe\t\nGST\n\tgenes,\tand\ttwo\tsuper\toxide\tdismutase\t(\nSOD)\n\tgenes.\tOne\tor\tmore\tof\nthe\t\nCYP
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SOD)\n\tgenes.\tOne\tor\tmore\tof\nthe\t\nCYP\n\tgenes\ttypically\tinclude:\t\nCYP2D6,\tCYP2C19,\tCYP3A4,\tCYP1A2,\tCYP29,\tCYP2B6,\n\tand\nCYP2E1.\n\tThere\tare\tthree\n\tcommon\t\nGST\n\tvariants:\tGSTM,\tGSTP1,\tand\tGSTT1.\tThe\tSOD\tgenes\nrepresented\tare\t\nSOD1\n\t(copper-zinc\tSOD)\tand\t\nSOD2\n\t(manganese-dependent\tSOD)\tthat\tprotect
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(copper-zinc\tSOD)\tand\t\nSOD2\n\t(manganese-dependent\tSOD)\tthat\tprotect\nagainst\tfree\tradicals\tgenerated\tduring\tbiotransformation.\tGene\tvariants\tin\tany\tof\tthe\tproteins\ninvolved\tin\tbiotransformation\tcan\tpotentially\talter\tthe\teffectiveness\tof\tthe\tprocess.\nCancer\n“Omic”\tclinical\tresearch\tand\tapplications\tare\tcurrently\tthe
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-0.0789145901799202, -0.023649953305721283, -0.03603522479534149, 0.0768948644399643, 0.0654410868883133, -0.05199433118104935, -0.0679008737206459, 0.0740242749452591, 0.010257099755108356, -0.10947024822235107, -0.03880223631858826, 0.08826496452093124, -0.029504144564270973, -0.03064310923218727, -0.04216042906045914, 0.07829221338033676, 0.047477539628744125, 0.00676388293504715, -0.020332833752036095, -0.017466580495238304, 0.04590094834566116, 0.04203833267092705, 0.09029003232717514, -0.028649577870965004 ]
Cancer\n“Omic”\tclinical\tresearch\tand\tapplications\tare\tcurrently\tthe\n\tmost\tadvanced\tfor\tcancer\tcompared\twith\nother\tchronic\tdiseases.\tThe\tinfluence\tof\tepigenetic\tmarks\ton\tgene\texpression\tis\tdirectly\tassociated\nwith\tthe\tdevelopment\tof\tcancer\tand\tits\tcharacteristic\tunregulated\tgrowth.\tThe\texpression\tof
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oncogenes\t(tumor-promoting\tgenes)\tand\ttumor\tsuppressor\tgenes\tmust\tbe\tcarefully\torchestrated\tto\nmaintain\tnormal\tgrowth\tand\tdevelopment.\tOncogenes\tare\ttypically\tsilenced\n\tepigenetically\tand\ntumor\tsuppressor\tgenes\tare\tactivated.\tIf\teither\tof\tthese\tsystems\tmalfunction,\tthe\trisk\tfor\tcancer
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could\tbe\tincreased.\tAn\texample\twould\tbe\ta\tmethyl\tgroup\tattaching\tto\ta\ttumor\tsuppressor\tgene\tby\nmistake\tand\tturning\toff\tits\texpression.\tOr,\tif\tsomeone\tlacked\tsufficient\tfolate\tin\tthe\tdiet,\tan\noncogene\tmay\tnot\tbe\tsufficiently\tturned\toff.\nAlthough\ttotal\tpersonalization\tof\tcancer\ttherapy,\n\tor\tany\tother\tmedical\ttherapy,\tfor\tan\tindividual\tis
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the\tmolecular\tlandscape\tin\twhich\tthe\tcancer\texists\t(i.e.,\tthe\tperson’s\tgenomic\tand\tepigenomic\nmakeup\tand\tthe\tmolecular\tcharacteristics\tof\tthe\tcancer\titself).\n\tMolecular\tdefects\tin\tthe\tindividual’s\ngenome\tand\tepigenome,\tand\tin\tthe\tcancer\titself,\tcan\tprovide\tvaluable\tinformation\tabout\tpotential\ntherapeutic\ttargets.\tSee\t\nLuoh\tand\tFlaherty\t(2018)
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therapeutic\ttargets.\tSee\t\nLuoh\tand\tFlaherty\t(2018)\n\tfor\tan\toverview\tof\tthe\ttypes\tof\tcancers\tbeing\nstudied\tand\ttreated\tusing\tthis\tapproach.\nGene\tvariants\tand\tcancer\nWell-known\texamples\tof\tapplying\tgenomics\tto\tcancer\tinclude\tdetection\tof\tBRCA1\tand\tBRCA2\tgenes\nin\n\tdiagnosing\tbreast\tcancer\tand\tthe\thMLH1\tand\thMSH2\tgenes\tin\tdiagnosing\thereditary
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nonpolyposis\tcolorectal\tcancer\t(HNPCC).\tGenetic\ttesting\tis\talso\tavailable\tfor\tdetecting\tsusceptibility\nto\tthese\ttypes\tof\tcancer.\tGenomic\ttesting\tis\talso\tbeing\tused\tto\tdistinguish\tspecific\ttumor\ncharacteristics\tto\thelp\tdifferentiate\tone\tcancer\tfrom\tanother.\tGenetic\tdiagnostics\thelp\tdetermine\nwhich\ttherapeutic\tapproach
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which\ttherapeutic\tapproach\n\twill\tlikely\tbe\tsuccessful\tand,\tduring\ttherapy,\thelp\tdetect\tearly\ttreatment\nfailure.\tAs\toptions\tfor\tearly\tdetection\tand\tprevention\temerge,\ttailorerd\tdiet-and-lifestyle\toptions\twill\nbecome\tcommon\tin\ttreatment\tof\tcancer.\nEpigenetics\tand\tcancer
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become\tcommon\tin\ttreatment\tof\tcancer.\nEpigenetics\tand\tcancer\nDietary\tnutrients\tand\tbioactive\tfood\tcomponents\tcan\taffect\tepigenetic\tprocesses\tin\tmultiple\tways,\nfrom\tproviding\tnutrients\tneeded\tto\tprotect\tagainst\tcancer\n\tto\tsuppressing\tgene\texpression\tof\tkey
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conducted\tfocuses\ton\tdietary\tnutrients\tand\tbioactive\tfood\tcomponents\n\tthat\tchange\tgene\texpression\nthrough\tepigenetic\tmechanisms\t(\nAndreescu\tet\tal,\t2018\n).\nWith\ttraditional\tnutrients,\ta\tmain\tfocus\tis\ton\tone-carbon\tmetabolism,\twhich\tsupplies\tthe\tmethyl\ngroups\tfor\tDNA\tmethylation\tand\thistone\tacetylation,\tin\taddition\tto\tnumerous\tother\timportant
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processes\tsuch\tas\tDNA\trepair.\tThese\tnutrients\tinclude\tfolate\tand\tfolic\tacid,\triboflavin,\tpyridoxine,\nvitamin\tB\n12\n,\tcholine,\tand\n\tmethionine.\tOther\tcommon\tdietary\tcomponents\tbeing\tstudied\tfor\ttheir\ncancer-protective\tproperties\tinclude\tdietary\tfiber,\tvitamin\tC,\tvitamin\tE,\tand\tselenium.\tIn\taddition\tto
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serving\tas\tligands\tfor\ttranscription\tfactors,\tpolyunsaturated\tfats\tare\tessential\tfor\tdownregulating
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the\texpression\tof\tthose\ttranscription\tfactors\tinvolved\tin\tswitching\ton\tproinflammatory\tgenes.\nExamples\tinclude\ttranscription\tfactors\n\tused\tfor\thepatic\tmetabolism\tof\tcarbohydrates,\tlipids,\tand\tbile\nacids\t(\nJump\tet\tal,\t2013\n).\nFor\tthe\tbioactive\tfood\tcomponents,\tidentification\tof\tbioactives\tfrom\tplants\tis\ta\tparticularly\tactive
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area\tof\tresearch\tbecause\ta\tsubstantial\tnumber\tof\thealth\tbenefits\thave\tbeen\treported\tfor\tthese\ncompounds.\tThe\tpolyphenol\tand\tglucosinolate\tcategories\tof\tphytonutrients\tare\tthe\tmost\tstudied\tfor\ncancer\ttreatment\n\tand\tprevention.\tEpigenetic\tchanges\tto\ttumor\tsuppressor\tgenes\tcan\tsilence\tthese\ngenes\tand\tlead\tto\tincreased\trisk\tof\ttumor\tdevelopment.
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genes\tand\tlead\tto\tincreased\trisk\tof\ttumor\tdevelopment.\nType\t2\tdiabetes\nType\t2\tdiabetes\tmellitus\t(T2DM)\tis\ta\tchronic\tdisorder\tthat\taccounts\tfor\tthe\tvast\tmajority\tof\nindividuals\twith\tdiabetes\t(see\t\nChapter\t29\n).\tT2DM\tis\tcomplex\tand\tresults\tfrom\tgene\tvariants\ninteracting\twith\tbioactive\tfood\tcomponents\tand\tother\tlifestyle
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interacting\twith\tbioactive\tfood\tcomponents\tand\tother\tlifestyle\n\ttriggers\tthat\tresult\tin\tepigenetic\nmodifications\tto\tthe\tgenome.\tThe\thallmarks\tof\tthis\ttype\tof\tdiabetes\tare\tinsulin\tresistance\tand\tfailure\nof\tthe\tinsulin-producing\tbeta\tcells\tof\tthe\tpancreas.\tNumerous\tstudies\thave\treported\tthe\tefficacy\tof
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interactions\tand\tmechanisms\tby\twhich\tthese\tinteractions\tepigenetically\tinfluence\tgene\texpression,\nwhich\twill\thelp\tin\tdeveloping\tnew\tand\teffective\tinterventions.\nGene\tvariants\tand\tT2DM\nA\tfew\trare\tmutations\thave\tbeen\tfound\tthat\tpredispose\tto\tT2DM,\tbut\n\tthey\tdo\tnot\texplain\tthe\thigh
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they\tdo\tnot\texplain\tthe\thigh\nprevalence\tof\tthe\tdisease.\tRather\tthan\tresulting\tfrom\ta\tsingle\tgene\tmutation,\tT2DM\tappears\tto\tbe\ndue\tto\tthe\tcontributions\tof\ta\tnumber\tof\tvariants\tinteracting\twith\tdiet-and-lifestyle\ttriggers.\tSome\tof\nthe\tvariants\tare\tin\tgenes\tthat\thave\tobvious\tconnections\tto\tglucose\thomeostasis,\tbut\tmany\tare\tnot.
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The\tfollowing\tvariants\tare\tamong\tthe\tmore\tpromising\tin\tterms\tof\tthe\tstrength\n\tof\ttheir\tassociation\nwith\trisk\tof\tdeveloping\ttype\t2\tdiabetes:\tTranscription\tfactor\t7-like\t2\t(\nTCF7L2\n),\tsolute\tcarrier\tfamily\n30\tmember\t8\t(\nSLC30A8\n),\tperoxisome\tproliferator\tactivated\treceptor\tgamma\t(\nPPARG\n),\tadiponectin\n(\nADIPOQ
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PPARG\n),\tadiponectin\n(\nADIPOQ\n),\tfat\tmass\tand\tobesity\tprotein/alpha-ketoglutarate\tdependent\tdioxygenase\t(\nFTO\n),\tclock\ncircadian\tregulator\t(\nCLOCK\n),\tand\tmelanocortin\t4\treceptor\t(\nMC4R\n).\t\nSLC30A8\n\tis\ta\tzinc\ttransporter\nthat\tis\trequired\tfor\tinsulin\tsynthesis\tand\tsecretion.\tThe\t\nADIPOQ,\tCLOCK,\tFTO,\n\tand\t\nMC4R\n\tvariants
[ -0.07168159633874893, -0.08071362972259521, -0.002690631430596113, -0.033216692507267, -0.06506714224815369, 0.06115883216261864, 0.05528765171766281, 0.06902444362640381, -0.011773592792451382, 0.06362028419971466, 0.07796678692102432, -0.023589547723531723, -0.06493082642555237, 0.06896758824586868, -0.038330044597387314, 0.014243734069168568, -0.04939396679401398, 0.046302277594804764, -0.013306240551173687, -0.07888878136873245, -0.011048906482756138, 0.057794440537691116, 0.020473860204219818, 0.010975044220685959, 0.01427491009235382, -0.008408013731241226, 0.01708357222378254, -0.03280637413263321, -0.047543901950120926, -0.07090534269809723, -0.0751657709479332, -0.014080493710935116, -0.005937796086072922, -0.04214344918727875, 0.026867277920246124, 0.03496833145618439, -0.07651908695697784, -0.010875239036977291, 0.06349162012338638, 0.03770419955253601, 0.05930304154753685, -0.1038278341293335, -0.04989156499505043, -0.007107681594789028, 0.07192464172840118, 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0.04513593018054962, -0.022499285638332367, 0.12568533420562744, 0.0977395549416542, -4.972976697104059e-8, 0.070683553814888, -0.008512342348694801, 0.018952304497361183, -0.03374650329351425, -0.009396842680871487, 0.006042082328349352, 0.07914994657039642, 0.042538244277238846, 0.012246279045939445, -0.09429680556058884, 0.0009473517420701683, 0.10332728922367096, -0.0054807658307254314, -0.03179996460676193, 0.08802185207605362, 0.005544443614780903, -0.08426304161548615, 0.008966062217950821, -0.01060304045677185, -0.11152070760726929, -0.04061786085367203, 0.008213147521018982, -0.03751377388834953, -0.0028559775091707706, 0.007380546536296606, -0.04024381563067436, -0.0154521269723773, -0.017231326550245285, 0.0448152981698513, 0.04145818203687668, 0.014042258262634277, -0.058331653475761414, 0.0022775456309318542, -0.061793964356184006, 0.02846052683889866, 0.05117441713809967, -0.0397757887840271, -0.03417505323886871, -0.06823453307151794, 0.10007601976394653, -0.06272436678409576, -0.038690753281116486, -0.04504203796386719, 0.04174330458045006, 0.06321655958890915, -0.061306100338697433, -0.03995931148529053, 0.07397163659334183, -0.009014060720801353, -0.05428317189216614, 0.007230303715914488, 0.04467659443616867, -0.061114754527807236, -0.05997031554579735, -0.10144534707069397, 0.03605034947395325, 0.0684957355260849, -0.039922527968883514, 0.021191149950027466, -0.06326743215322495, 0.010390227660536766, 0.0509662963449955, 0.12902456521987915, -0.01701711118221283 ]
ADIPOQ,\tCLOCK,\tFTO,\n\tand\t\nMC4R\n\tvariants\nare\tassociated\twith\tobesity\tand\tincreased\trisk\tfor\tdeveloping\tT2DM.\t\nPPARG\n\tis\ta\ttranscription\tfactor\ninvolved\twith\tlipid\tmetabolism\tand\tadipocyte\tdifferentiation\tthat\tregulates\tthe\texpression\tof\tmultiple\ngenes.\tIt\thas\tbeen\timplicated\tin\tdiabetes,\tobesity,\tcancer,\tand\tatherosclerosis.\tFor\tfurther\tdepth
[ -0.00035815348383039236, -0.0584377758204937, 0.05922902002930641, 0.007326338905841112, -0.09283463656902313, -0.016435254365205765, 0.11155574768781662, 0.04113280028104782, -0.011459015309810638, 0.03659940883517265, 0.08560045808553696, -0.020771583542227745, 0.013436192646622658, 0.021449513733386993, 0.000053772546380059794, -0.002861838322132826, -0.024385591968894005, 0.008905850350856781, -0.011648733168840408, -0.027528399601578712, 0.026505697518587112, 0.08097963780164719, 0.05735282227396965, 0.0034160539507865906, 0.0025686509907245636, 0.0051210965029895306, -0.018701085820794106, -0.01764388009905815, 0.021593473851680756, -0.029230153188109398, -0.13338270783424377, 0.08113124221563339, -0.024145573377609253, -0.022225212305784225, 0.01368625182658434, 0.018296437337994576, -0.04553328454494476, 0.03283099830150604, 0.006607865449041128, 0.026894167065620422, 0.03161966800689697, -0.15408462285995483, -0.06268364191055298, 0.016759837046265602, 0.0662715807557106, 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into\nany\tof\tthese\tvariants,\tvisit\tthe\tGene\twebsite\tfrom\tthe\tNational\tCenter\tfor\tBiotechnology\tInformation\nor\tthe\tGenetics\tHome\tReference\twebsite\tfrom\tthe\tNational\tInstitutes\tof\tHealth.\nTCF7L2\n\tis\tinvolved\twith\tinsulin\tsecretion\tand\texhibits\tthe\tstrongest\tassociation\tby\tfar\twith\nsusceptibility\tto\tT2DM.\tThe\t\nTCF7L2
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susceptibility\tto\tT2DM.\tThe\t\nTCF7L2\n\tgene\tencodes\ta\ttranscription\tfactor\tthat\tplays\ta\tkey\trole\tin\tthe\nWNT\tsignal\ttransduction\n\tpathway.\tFurther,\t\nTCF7L2\n\thas\tbeen\tdetected\tin\tmultiple\tpopulations.\tIn\nstudies\twith\tIndian\t(\nChandak\tet\tal,\t2007\n),\tChinese\tHan\t(\nDou\tet\tal,\t2013\n),\tJapanese\t(\nHorikoshi\tet\tal,\n2007\n),\tMexican\tAmerican\t(
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),\tJapanese\t(\nHorikoshi\tet\tal,\n2007\n),\tMexican\tAmerican\t(\nLehman\tet\tal,\t2007\n),\tAfrican\t(\nYako\tet\tal,\t2016\n),\tand\twhite\tEuropean\n(\nGroves\tet\tal,\t2006\n)\tpopulations,\tthe\tvariant\toccurred\tfrequently\tand\tincreased\tthe\trisk\tof\tT2DM\tby\n30%\tto\t50%.\t\nTCF7L2\n\thas\talso\tbeen\n\tfound\tto\tpredispose\tindividuals\twith\tmetabolic\tsyndrome\tto\ndeveloping\tT2DM\t(
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developing\tT2DM\t(\nKatsoulis\tet\tal,\t2018\n).\nEpigenetics\tand\tT2DM\nStudies\thave\tlong\tsuggested\tthat\tT2DM\tis\tstrongly\tassociated\twith\tdiet-and-lifestyle\tchoices,\tmost\nnotably\tfood\tchoices\t(especially\tdietary\tfat)\tand\texercise\thabits.\tT2DM\thas\tbeen\tassumed\tto\tbe\ngenetic\tin\torigin\tbut,\twith\tthe\texception\tof\t\nTCF7L2,\n\tthe\tlarge\tnumber\tof\tgene
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TCF7L2,\n\tthe\tlarge\tnumber\tof\tgene\n\tvariants\tthat\thave\nbeen\tidentified\tappear\tto\tweakly\tcontribute\tto\tT2DM\tsusceptibility.\tThe\tanswers\tappear\tto\tbe\t(1)\nthere\tare\tmultiple\tgenes\tinvolved\tand\t(2)\tepigenetic\tmechanisms\tinvolving\tdiet-and-lifestyle\ttriggers\nare\timportant\tcontributors.\tResearch\tto\tdetect\tepigenetic\tchanges\tin\tresponse\tto\tnutrients\tand
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bioactive\tfood\tcomponents\tis\tin\tprogress.\nA\tnutrient-sufficient\tantiinflammatory\tdiet\n\tin\twhich\tcarbohydrate\tand\tfat\tconsumption\tis\ncontrolled\tfor\tquantity\tand\tquality\tcontinues\tto\tbe\ta\tcornerstone\tof\tT2DM\tcare.\tIncreasingly,\ta\tfocus\nis\tbeing\tplaced\ton\tthe\tincorporation\tof\ta\tvariety\tof\tphytonutrients\tinto\tthe\tdiet.\tResults\tfrom\tthe
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Nurses’\tHealth\tStudy\t(NHS)\tand\tits\tfollow-up\t(NHS\tII)\t(\nSun\tet\tal,\t2015\n),\tas\twell\tas\tthe\tHealth\nProfessionals\tFollow-Up\tStudy\t(\nWedick\tet\tal,\t2012\n),\tsuggest\n\tthat\tregular\tconsumption\tof\nphytonutrient-rich\tplant\tfoods\thelped\tlower\tthe\trisk\tof\tdeveloping\tT2DM.
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In\taddition\tto\tdiet\tand\texercise,\tother\tdaily\tlifestyle\tchoices\tinfluence\tthe\tphysiologic\timbalances\nthat\tlead\tto\tchronic\tinflammation\tand\tmust\tbe\tincorporated\tinto\tlifestyle\tchange\tprograms\tif\tthe\npositive\tchanges\tare\tto\tbe\tsustained\tlong\tterm.\tExamples\tinclude\tchronic\tpsychological\tand\nphysiological
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physiological\n\tstress\tand\texposure\tto\tchemicals\tand\ttoxins.\tHopefully,\thealth\tcare\twill\tmove\ttoward\napproaches\tfor\tT2DM\tand\tfor\tchronic\tdisease\tin\tgeneral\tthat\ttarget\tthe\tunderlying\tchronic\ninflammation\talong\twith\tcontemporary\tneuroscience-based\tbehavioral\tchange\tprograms\tthat\tenable
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those\tat\trisk\tto\taddress\ttheir\tbarriers\tto\tmaking\thealthy\tlifestyle\tchoices.\nFor\tmore\tin-depth\tinformation\tabout\tthe\tgenomic\n\tand\tepigenetic\taspects\tof\tT2DM,\tsee\trecent\nreviews\tby\t\nSilveira\tet\tal\t(2019)\n,\t\nXue\tet\tal\t(2018)\n,\tand\t\nOrtega\tet\tal\t(2017)\n.\nObesity\nObesity\tis\tusually\tindicated\tby\tbody\tmass\tindex\t(BMI),\twhich\tis\tmeasured\tin\tkg/m\n2
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2\n.\tIt\tis\timportant\tto\nassess\teach\tperson\tindividually,\tincluding\tweight\thistory,\twaist\tcircumference,\tand\tbody\tcomposition\nas\tpeople\twith\tlarger\tbody\tsizes\tcan\tbe\tmetabolically\thealthy\n\tin\tsome\tcases.\tDifferent\tcountries\tuse
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somewhat\tdifferent\tBMI\tscores\tto\tdefine\tobesity,\tbut\ta\tcommon\tglobal\tstandard\tis\tthat\tset\tby\tthe\nWorld\tHealth\tOrganization\t(WHO),\twhich\tclassifies\ta\tBMI\tof\t≥25\tkg/m\n2\n\tin\tadults\tas\noverweight/preobese,\ta\tBMI\t≥30\tkg/m\n2\n\tas\tobese,\tand\ta\tBMI\t≥40\tkg/m\n2\n\tas\textremely\tobese.\tWHO
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2\n\tas\tobese,\tand\ta\tBMI\t≥40\tkg/m\n2\n\tas\textremely\tobese.\tWHO\nhas\talso\tset\tBMI\tstandards\tfor\tchildren\tup\tto\t5\tyears\told\tand\t5\tto\t19\tyears\told.\tThe\tprevalence\n\tof\nobesity\tis\tsteadily\trising.\tIn\tthe\tUnited\tStates\tthe\t2015\tto\t2016\tNational\tHealth\tand\tNutrition\nExamination\tSurvey\tfound\t39.8%\tof\tadults\tand\t18.5%\tof\tyouth\tto\tbe\tobese\t(\nHales\tet\tal,\t2017\n).
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Hales\tet\tal,\t2017\n).\nIn\taddition\tto\tbeing\ta\tstorage\torgan\tready\tto\tprovide\tfor\tfuture\tenergy\tneeds,\tadipose\ttissue\tis\tan\nactive\tmetabolic\ttissue\tthat\tis\timportant\tin\twhole\tbody\tenergy\tbalance.\tAdipose\ttissue\tsecretes\nadipokines,\n\twhich\tare\tcell\tsignaling\tproteins.\tAdipokine\texamples\tinclude\tleptin,\tadiponectin,\tand
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proinflammatory\tadipokines,\tsuch\tas\tthe\tinterleukins\tand\ttumor\tnecrosis\talpha\tcytokines\tdiscussed\nin\tthe\ttype\t2\tdiabetes\tsection.\tWhen\tleptin\t(\nLEP\n)\tbinds\tto\tleptin\treceptors\t(\nLEPR\n)\tin\tthe\nhypothalamus,\tbinding\tsends\tthe\tsignal\tof\tsatiety,\tfollowed\tby\ta\treduction\tin\tthe\tdesire\tto\teat\tand\ta\nstimulated\tthermogenesis.
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stimulated\tthermogenesis.\n\tThe\tfoundational\twork\twas\tdone\tin\tmouse\tmodel\tsystems\tand\nsubsequently\tfound\tto\tbe\toperative\tin\thuman\tbeings\t(\nGhilardi\tet\tal,\t1996\n;\t\nDulloo\tet\tal,\t2002\n).\nAdiponectin\tis\ta\tprotein\thormone\tadipokine\tencoded\tby\tthe\t\nADIPOQ\n\tgene\tand\tproduced\tby
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ADIPOQ\n\tgene\tand\tproduced\tby\nadipocytes.\tIt\tappears\tto\tbe\timportant\tfor\tmetabolic\tbalance,\tparticularly\tin\treference\tto\tthe\tinsulin\nresistance,\toxidative\tstress,\tand\tchronic\tinflammation\n\tcharacteristic\tof\tthe\tmetabolic\tsyndrome\n(\nAchari\tand\tJain,\t2017\n).\tIn\tparticular\tthe\tbalance\tbetween\tadiponectin\tand\tleptin\thas\tbeen
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0.00750906765460968, -0.026200685650110245, -0.005354065913707018, 0.04797733575105667, 0.06169779971241951, -0.10111043602228165, 0.040635041892528534, 0.05159681290388107, 0.031207531690597534, -0.10009618103504181, -0.029392408207058907, 0.09752602875232697, 0.021918751299381256, -0.05409513786435127, -0.06429936736822128, 0.026757463812828064, 0.06342814117670059, 0.030822807922959328, 0.004991296213120222, 0.0118238041177392, 0.06841286271810532, 0.12563389539718628, 0.08570641279220581, 0.015817491337656975 ]
).\tIn\tparticular\tthe\tbalance\tbetween\tadiponectin\tand\tleptin\thas\tbeen\ncorrelated\twith\tthe\tobesity\tcomponent\tof\tmetabolic\tsyndrome.\tA\tdecrease\tin\tthe\tadiponectin/leptin\nratio\tincreases\tthe\trisk\tof\tobesity,\tinflammation,\tand\tdevelopment\tof\tthe\tmetabolic\tsyndrome\n(\nFrühbeck\tet\tal,\t2017\n).\nADIPOQ\n\tis\ta\tgene\tof\tinterest\tbecause\tof\tits\tassociation
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).\nADIPOQ\n\tis\ta\tgene\tof\tinterest\tbecause\tof\tits\tassociation\n\twith\tobesity\tbut\talso\tpotentially\tfor\ttype\t2\ndiabetes\tand\tmetabolic\tsyndrome.\tOne\tof\tthe\tSNPs\tin\tthis\tgene\t(-11391G>A,\trs17300539)\tappears\nto\tlink\tincreased\tlevels\tof\tadiponectin\twith\tdecreased\trisk\tof\tobesity.\tIn\twhite\tAmericans,\tthose\twith
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0.07266528904438019, -0.0020008350256830454, 0.04730789363384247, 0.042462874203920364, -5.009430026348127e-8, 0.04112200438976288, -0.016607191413640976, -0.020016467198729515, -0.03185386210680008, 0.04207513853907585, 0.0008865727577358484, 0.03784360736608505, 0.007899937219917774, 0.018087856471538544, -0.04891572147607803, 0.01025386992841959, 0.07590659707784653, -0.09669596701860428, -0.05824953317642212, 0.10023284703493118, 0.033685605973005295, -0.005462202243506908, 0.15478909015655518, -0.04646069556474686, -0.035470545291900635, -0.002829092787578702, 0.10889708995819092, -0.014992166310548782, -0.028113815933465958, -0.06416656821966171, 0.026690546423196793, -0.023959292098879814, -0.013494018465280533, 0.015054893679916859, -0.009574968367815018, 0.027857381850481033, -0.025380073115229607, -0.0032583761494606733, -0.04376586899161339, -0.06009514629840851, 0.07733147591352463, -0.05681289732456207, -0.023717280477285385, 0.010843022726476192, 0.11338338255882263, 0.05744379758834839, 0.02886028401553631, -0.019996101036667824, 0.07012485712766647, 0.03669393062591553, -0.09753545373678207, 0.023767296224832535, 0.0932142585515976, 0.039047904312610626, -0.05741781368851662, -0.04502293840050697, 0.11737555265426636, -0.005027445498853922, -0.03805205598473549, -0.025700636208057404, -0.0018695808248594403, 0.05003376305103302, 0.08515019714832306, -0.014826774597167969, 0.03242916241288185, 0.1167379692196846, 0.08051566034555435, 0.051609329879283905, -0.03067413903772831 ]
one\tor\tmore\tcopies\tof\tthe\tvariant\tallele\t(A)\thad\televated\tadiponectin\tlevels\tand\tdecreased\tweight,\nwaist\tand\thip\tcircumference,\tand\tBMI\t(\nWarodomwichit\tet\tal,\t2009\n).\tThese\tresearchers\tfurther\ndetected\ta\tgene-diet\tinteraction\tbetween\tthe\tvariant\tallele\t(A)\tand\tmonounsaturated\tfat\t(MUFA).
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When\tMUFA\tintake\twas\tequal\tto\tor\tgreater\tthan\t13%\tof\ttotal\tenergy,\tthose\twith\tone\tor\tmore\tcopies\nof\tthe\tA\tallele\t(AA\tor\tAG\tgenotype)\thad\ta\tlower\tBMI\tcompared\twith\tindividuals\twith\tthe\tGG\ngenotype\t(2\tcopies\tof\tthe\tnon-variant\tG\tallele).\tNo\teffect\tof\tthe\tA\tallele\twas\tseen\n\tfor\twaist
[ -0.012306759133934975, -0.015460685826838017, 0.0476822666823864, -0.08200876414775848, -0.08745574951171875, 0.022694449871778488, 0.08510822057723999, 0.03463764488697052, -0.0398009829223156, 0.0439547523856163, 0.11612711101770401, -0.057435572147369385, -0.008286621421575546, 0.03021443448960781, -0.011104810051620007, 0.02914685755968094, 0.027985362336039543, 0.01127078477293253, -0.06705015897750854, -0.09242165833711624, 0.024155784398317337, 0.0932496041059494, 0.05252452567219734, -0.013721710070967674, -0.011577589437365532, -0.008632954210042953, -0.021494846791028976, 0.027873214334249496, 0.08614858984947205, -0.059248898178339005, -0.12091302871704102, 0.1070718839764595, -0.03613985329866409, 0.002733883447945118, 0.01988891325891018, -0.03752321004867554, -0.0788300484418869, 0.021193236112594604, 0.06460762768983841, -0.018656108528375626, 0.04493529349565506, -0.054407428950071335, -0.04434268921613693, 0.03738086298108101, 0.02691248245537281, 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for\twaist\ncircumference,\tinsulin\tresistance\tor\tfor\tsaturated\tfat\tor\tpolyunsaturated\tfats.\tOther\tresearchers\nhave\treported\tincreased\trisk\tof\tobesity\tin\tthe\tpresence\tof\tSNPs\tin\t\nADIPOQ\n\tin\tthe\tNorth\tIndian\nPunjabi\tpopulation\t(\nKaur\tet\tal.,\t2018\n)\tand\tin\tthe\tTunisian\tpopulation\t(\nZayani\tet\tal,\t2018\n).\tThese\ninteresting\tfindings\twith\t\nADIPOQ
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Zayani\tet\tal,\t2018\n).\tThese\ninteresting\tfindings\twith\t\nADIPOQ\n\twill\tlikely\tcontinue\tto\tbe\tstudied\tin\tmultiple\tpopulations\tand\n\tunder\nvarying\tdietary\tconditions.\nAs\twith\tleptin,\tmuch\tof\tthe\tinitial\twork\twith\tadiponectin\thas\tbeen\tcarried\tout\tusing\tmouse\tmodel
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systems,\twith\tresearch\tin\thuman\tbeings\tfollowing\tmore\trecently.\tGiven\tthe\tapparent\timportance\tof\nthese\tgenes\tin\tenergy\tmetabolism,\tthe\tlack\tof\tconsistency\tis\tlikely\tdue\tto\ta\tlarge\tvolume\tof\tresearch\nbut\tvery\tfew\tpolymorphisms\tare\tlinked\tto\tincreased\trisk\tof\tdeveloping\n\tobesity\tacross\tmultiple
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obesity\tacross\tmultiple\npopulations.\tAdditionally,\tthe\tcomplexity\tof\tobesity\tand\tthe\tmultitude\tof\tmolecules\tinvolved\thas\nmade\tit\tchallenging\tto\tuntangle\tthe\tmultiple\tinteractions\tthat\tincrease\tor\tdecrease\trisk\tof\ndeveloping\tobesity\t(\nJagannadham\tet\tal,\t2016\n).\tA\trecent\treview\tby\t\nUnamuno\tet\tal\t(2018)\n\tprovides
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).\tA\trecent\treview\tby\t\nUnamuno\tet\tal\t(2018)\n\tprovides\ninsight\tinto\tthe\tcomplexity\tof\tdysfunctional\tadipose\ttissue\tand\tthe\tensuing\tdysregulation\n\tof\nadipokine\tsecretion,\twhich\tleads\tto\tchronic\tinflammation\tand\tincreased\trisk\tof\tchronic\tdisorders\nsuch\tas\tinsulin\tresistance,\ttype\t2\tdiabetes,\tatherosclerosis,\tcancer,\tand,\tmost\tlikely,\tobesity.
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increased\ttoxin\tload\tand\tabundance\tof\thigh-calorie\tprocessed\tfoods,\tto\tunderstanding\tthe\tcomplex\nbehavioral\taspects\tof\twhy\twe\tmake\tthe\tfood\tchoices\twe\tdo.\tThe\tepigenetic\tmechanisms\tthat\tlink\nobesity\tto\tincreased\trisk\tof\tT2DM\tand\tcardiovascular\tdisease\tadd\tyet\tmore\tcomplexity.\tClearly,\twhy\nand\thow
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and\thow\n\thumans\tbecome\tobese\tis\tmultifaceted\tand\tmultiple\tdisciplines\twill\tbe\tinvolved\tin\tdefining\nthe\tmechanisms\tand\tfinding\teffective\tsolutions.\tThe\taddition\tof\tcontemporary\tneuroscience\tand\nbehavioral\tresearch\tto\tthe\tsearch\tfor\tanswers\tas\tto\twhy\tand\thow\twe\tbecome\tobese\tis\texpanding\tour\ninsight\tinto\tthis\tchallenging\tdilemma\t(see\t\nChapter\t20\n).
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insight\tinto\tthis\tchallenging\tdilemma\t(see\t\nChapter\t20\n).\nThe\tsections\tthat\tfollow\thighlight\tgenes\tand\tgene\tvariants\n\tthat\tare\tamong\tthose\twith\ta\tstronger\nassociation\twith\tobesity\tthan\tmost\tvariants,\talong\twith\ta\tdiscussion\tof\tthe\trole\tof\tepigenetics\tin\nobesity.\tThe\tfact\tthat\tenvironmental\tfactors\tplay\ta\tmajor\trole\tin\ttriggering\tthe\tdevelopment\tof
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0.08229663968086243, 0.03746393695473671, 0.018767910078167915, -0.048097092658281326, 0.09756000339984894, 0.060269590467214584, -0.06261426955461502, 0.01732732728123665, 0.06331854313611984, -0.0028413664549589157, -0.02895866520702839, -0.027049023658037186, 0.10742689669132233, -0.012504949234426022, -0.0609622485935688, -0.04838487505912781, 0.060870081186294556, 0.048322759568691254, 0.055665023624897, -0.03060171566903591, 0.012757604010403156, 0.10784178227186203, 0.050745245069265366, 0.0643802285194397, -0.02158317156136036 ]
genes\tthat,\twhen\tmutated,\tlead\tto\nsevere\tobesity.\tExamples\tof\twell-studied\tgene\tvariants\tassociated\twith\tmonogenic\tobesity\tinclude\nmutations\tin\t\nMC4R\n\t(melanocortin-4\treceptor),\t\nLEP\n,\tand\t\nLEPR.\n\tIn\tcontrast,\t\npolygenic\n\t(multigene)\nobesity\thas\tbeen\treferred\tto\tas\t“common\tobesity”\twhere\tmultiple\tgenes\tand\tenvironmental\ttriggers
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are\tinvolved.\tThis\tbasis\tfor\tobesity\toccurs\tfrequently.\tIn\tcommon\tobesity,\n\tmutation\tin\ta\tsingle\tgene\ncontributes\tonly\ta\tsmall\tdegree\tof\trisk;\tdevelopment\tof\tthe\tsusceptibility\tto\tbecoming\tobese\tis\nstrongly\tdependent\ton\tthe\tinteraction\twith\tenvironmental\ttriggers.\tHowever,\tthe\trecent\tfinding\tby\nFairbrother\tet\tal\t(2018)\n\tthat\tmutations\tin\t\nMC4R
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0.04250958561897278, -0.0028888152446597815, 0.011122612282633781, 0.055795762687921524, 0.06165602058172226, -0.048981841653585434, 0.011577499099075794, 0.08001348376274109, -0.02054833434522152, -0.04955793544650078, -0.023615911602973938, 0.09604746848344803, 0.013546871952712536, -0.07851782441139221, -0.060205429792404175, 0.08128830790519714, 0.07901649177074432, 0.045910608023405075, -0.043637752532958984, -0.007128160446882248, 0.09891900420188904, 0.04321444034576416, 0.1035105511546135, -0.0027334250044077635 ]
constitute\ta\tcontinuum\tof\tphenotypes\tranging\tfrom\tsilent\tto\tmild\tto\tsevere\teffects\ton\tfunction.\nHowever,\tbe\taware\tthat\tthis\ttype\tof\tclassification\tis\tin\tthe\tliterature\tand\tcan\tcause\tconfusion.\tIn\tthis\nsection\tthe\tfocus\twill\tbe\ton\twhat\thas,\tto\tdate,\tbeen\ttermed\tcommon\tobesity\tinvolving\n\tmultiple\tgenes\nand\tmultiple\tenvironmental\ttriggers.
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multiple\tgenes\nand\tmultiple\tenvironmental\ttriggers.\nAlso\tnot\tsurprising\tis\tthe\tlarge\tnumber\tof\tgenes\tidentified\tas\tcontributors\tto\tthe\tpredisposition\tfor\nobesity,\tparticularly\tsince\tGWAS\tstudies\thave\tcome\tto\tbe\tused\troutinely\tin\tthe\tsearch\tfor\tgenes\tof
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interest\tand\ttheir\tpolymorphisms.\tOne\tgene\tthat\thas\tfor\tseveral\tyears\tbeen\tfound\tto\thave\ta\tstrong\nassociation\twith\tcommon\tobesity\tand\tto\toccur\n\tfrequently\tin\tmultiple\tpopulations\tis\t\nFTO\n\t(\nLoos\tand\nYeo,\t2014\n).\tThis\tgene\tencodes\tthe\tfat\tmass\tand\tobesity\tprotein\t(an\talpha-ketoglutarate\tdependent
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dioxygenase).\tIts\tmechanism\tof\taction\tappears\tto\tbe\trelated\tto\tthe\tregulation\tof\tadipose\ttissue\ndevelopment,\twhich\tsuggests\tbody\tcomposition\tis\taffected\t(\nYang\tet\tal,\t2017\n).\tVariations\tin\tthe\t\nFTO\ngene\thave\tbeen\tfound\tin\tmultiple\tpopulations.\tIts\teffect\n\tis\tgreater\tin\tEuropean\tdescendants\tthan\tin\nAfrican\tor\tAsian\tpopulations\t(\nLoos\tand\tYeo,\t2014
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African\tor\tAsian\tpopulations\t(\nLoos\tand\tYeo,\t2014\n;\t\nMerritt\tet\tal,\t2018\n).\nGene–diet\tinteractions\thave\tbeen\treported\tfor\tSNPs\tin\tthe\t\nFTO\n\tgene.\tData\tfrom\ta\tcross-sectional\nstudy\tfound\tthat\tthose\twith\tthe\tA\tallele\tof\t\nFTO\n\tgene\twho\treported\thigh\tlevels\tof\tdietary\tfat\tand\tlow
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FTO\n\tgene\twho\treported\thigh\tlevels\tof\tdietary\tfat\tand\tlow\nlevels\tof\tphysical\tactivity\thad\thigher\tBMI\tvalues\tthan\tthose\twith\tthe\tA\tallele\twho\n\treported\ta\tlower-\nfat\tdiet\t(\nSonestedt\tet\tal,\t2009\n).\tA\tlow-carbohydrate\tdiet\tappeared\tto\tattenuate\tthe\teffect\tof\tthe\thigh-\nfat\tdiet\tin\tthose\twith\tthe\trisk\tallele.\t\nLappalainen\tand\tcolleagues\t(2012)
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0.06710661202669144, 0.03962850943207741, 0.025371139869093895, 0.032943062484264374, -4.931061425850203e-8, -0.016442978754639626, -0.03554626554250717, -0.04638222977519035, -0.0023251560050994158, 0.05670502036809921, -0.0049234237521886826, 0.04221241921186447, -0.0013676966773346066, 0.011567851528525352, -0.028387419879436493, 0.03922946751117706, 0.08534280210733414, -0.050768785178661346, -0.028255248442292213, 0.03865443170070648, 0.02255048230290413, 0.022961363196372986, 0.11106476932764053, -0.04201078787446022, -0.08652886748313904, -0.029458578675985336, 0.07018765062093735, -0.03625849261879921, -0.010549928061664104, -0.03678020462393761, 0.010348417796194553, -0.02831178717315197, -0.027931619435548782, -0.01987423188984394, -0.0022326528560370207, 0.10147060453891754, -0.038033753633499146, -0.003171465592458844, -0.0403599813580513, 0.013520396314561367, 0.043839894235134125, -0.024766305461525917, -0.0540090873837471, -0.03984977304935455, 0.1505420058965683, 0.036577459424734116, 0.012539959512650967, -0.0031930371187627316, 0.06989789754152298, 0.06924756616353989, -0.07280818372964859, -0.017200998961925507, 0.06375245749950409, 0.02911428175866604, -0.015236879698932171, -0.02886345237493515, 0.023089809343218803, -0.012647290714085102, -0.0346650667488575, -0.06789346039295197, 0.005264344625174999, 0.060816723853349686, 0.04184740409255028, 0.039420004934072495, 0.04636281356215477, 0.08146938681602478, 0.08415374159812927, 0.07782634347677231, -0.005926998797804117 ]
Lappalainen\tand\tcolleagues\t(2012)\n\tinvestigated\tthe\teffect\tof\tthis\nsame\tSNP\ton\tBMI\tin\tsubjects\tin\tthe\tFinnish\tDiabetes\tPrevention\tStudy.\tThis\tgroup\talso\tfound\nelevated\tBMI\tvalues\tin\tthose\tconsuming\ta\thigh-fat\tdiet.\tMore\trecently\t\nVimaleswaran\tet\tal\t(2016)\nreported\ta\tgene–diet\tinteraction\tin\ta\tsecond\t\nFTO
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reported\ta\tgene–diet\tinteraction\tin\ta\tsecond\t\nFTO\n\tSNP\tin\tan\tAsian\tIndian\tpopulation.\tIndividuals\twith\nthe\tSNP\twho\talso\tconsumed\ta\thigh-carbohydrate\tdiet\thad\tincreased\trisk\tof\tbeing\tobese.\tPhysical\ninactivity\tseemed\tto\talso\tinfluence\tobesity\trisk\tin\tthese\tindividuals.
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Two\tother\tgenes\tthat\tinfluence\tnot\tonly\tobesity\tbut\talso\tinsulin\tsensitivity/resistance\tare\tthe\nsuppressor\tof\tcytokine\tsignaling\n\t3\t(\nSOCS3\n)\tgene\tand\tthe\tperoxisome\tproliferator-activated\treceptor\ngamma\t(\nPPARG2\n)\tgene.\t\nSOCS3\n\tinhibits\tcytokine\tsignal\ttransduction\t(part\tof\tthe\tinflammatory
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inhibits\tcytokine\tsignal\ttransduction\t(part\tof\tthe\tinflammatory\nresponse)\tthrough\tthe\tJanus\tkinase/signal\ttransducer\tand\tactivator\tof\ttranscription\t(JAK/STAT)\nsignaling\tpathway.\t\nSOCS3\n\tis\tfrequently\toverexpressed\tin\tobesity\tand\tdiabetes\t(\nGalic\tet\tal,\t2014\n).\tIn\nan\t\nexpression\tgenome-wide\tassociation\tstudy\t(eGWAS)\n,\t\nXu\tet\tal\t(2018)
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expression\tgenome-wide\tassociation\tstudy\t(eGWAS)\n,\t\nXu\tet\tal\t(2018)\n\tfound\tthat\tthe\t\nSOCS3\npromoter\twas\thypomethylated\tin\tobese\tindividuals.\tWithin\tthis\tlow-methylated\t\nSOCS3\n\tgroup,\tthose\nwho\thad\thad\tfive\tor\tmore\tmajorly\tstressful\tlife\tevents\twere\tat\tincreased\trisk\tof\tobesity.\nThe\t\nPPARG
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The\t\nPPARG\n\tgene\tis\ta\tnuclear\treceptor\tthat\tfunctions\tas\ta\ttranscription\tfactor\tand\tis\ta\tkey\ncontributor\tto\tfat\tcell\tformation.\tIt\tis\tfrequently\treferred\tto\tas\tthe\t“master\tregulator”\n\tof\nadipogenesis\tand\tdifferentiation\t(\nMukherjee\tet\tal,\t1997\n).\tGene–diet\tinteractions\tfor\tthe\tPPARG\tgene\nhave\tbeen\treported,\toriginally\tby\t\nMemisoglu\tet\tal\t(2003)
[ -0.029068319126963615, -0.06267914175987244, 0.06237773224711418, -0.013095471076667309, -0.14170609414577484, 0.022808320820331573, 0.05218261852860451, 0.03134765103459358, -0.019520791247487068, 0.03971615806221962, 0.10909100621938705, -0.022007731720805168, -0.008102543652057648, -0.02058934047818184, -0.049846190959215164, -0.010544219985604286, -0.0036839221138507128, -0.008344784379005432, 0.0047124349512159824, -0.0852377861738205, 0.01989228092133999, 0.06286133080720901, 0.07401534169912338, -0.012926304712891579, 0.005372713319957256, -0.025671064853668213, -0.0641712173819542, -0.014934933744370937, -0.009518240578472614, -0.04142172634601593, -0.1139969676733017, 0.04948669299483299, -0.009404735639691353, -0.01202272716909647, 0.01701539009809494, 0.016492517665028572, -0.042467594146728516, 0.0368252694606781, 0.0688425600528717, -0.006930339150130749, 0.056493133306503296, -0.12910129129886627, -0.040853627026081085, 0.0019431348191574216, 0.08514577895402908, 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0.0030010880436748266, 0.031788259744644165, 0.03911940008401871, 0.07332512736320496, 0.05612746998667717, -5.8347403353309346e-8, 0.05484791472554207, -0.023646358400583267, -0.05264316499233246, -0.0118720019236207, 0.03752046450972557, -0.004918125458061695, 0.03712499886751175, -0.008305558934807777, -0.007249790709465742, -0.03439702093601227, 0.05292712524533272, 0.0677032619714737, -0.06261147558689117, -0.06116371229290962, 0.07566143572330475, -0.006514973472803831, -0.018027693033218384, 0.07639383524656296, -0.05249149724841118, -0.10176587849855423, -0.00522019574418664, 0.07021666318178177, 0.009359186515212059, -0.0072705731727182865, -0.05482512712478638, 0.03925902768969536, -0.02790042571723461, 0.04100244864821434, 0.00288063264451921, 0.023094575852155685, 0.06124836578965187, -0.030042164027690887, 0.00910848006606102, -0.03265853598713875, -0.00150196289177984, 0.046061355620622635, -0.03484223783016205, -0.029720336198806763, -0.013307117857038975, 0.14700447022914886, 0.013335445895791054, 0.009939607232809067, -0.013927741907536983, 0.08688851445913315, 0.04557749256491661, -0.0513705350458622, -0.04918597266077995, 0.08380575478076935, 0.011973636224865913, -0.043210163712501526, -0.012542221695184708, 0.0714048519730568, -0.020181652158498764, -0.02775120921432972, -0.06958406418561935, 0.021767063066363335, 0.09538451582193375, 0.01057456061244011, -0.0022722305729985237, -0.003831178182736039, 0.11502963304519653, 0.075566366314888, 0.11103800684213638, -0.04346456751227379 ]
have\tbeen\treported,\toriginally\tby\t\nMemisoglu\tet\tal\t(2003)\n\tand\tmore\trecently\tby\t\nRodrigues\tand\ncolleagues\t(2017)\n.\tIn\ta\tsubgroup\tof\tthe\tNurses’\tHealth\tStudy,\tMemisoglu\tand\tcolleagues\ninvestigated\tthe\tinteraction\tbetween\tthe\t\nPPARG2\n\tPro12Ala\tSNP\t(the\tPro\tallele\tis\tthe\twild-type\tallele\nand\tthe\tAla\tallele
[ -0.07068594545125961, -0.06672705709934235, 0.10770068317651749, -0.05455217510461807, -0.09000538289546967, 0.05704938620328903, 0.025628644973039627, -0.04319338500499725, 0.014473222196102142, 0.02217617817223072, 0.09708556532859802, -0.006914792116731405, -0.021357018500566483, -0.02864452823996544, -0.09091377258300781, 0.03423789143562317, -0.0241212397813797, 0.004957511555403471, -0.0018607662059366703, -0.028426047414541245, -0.015278581529855728, 0.01569351740181446, 0.06472474336624146, -0.0005703599890694022, -0.006935787852853537, -0.016454558819532394, -0.04897715523838997, -0.0008379981736652553, -0.028499498963356018, -0.03463705629110336, -0.10330090671777725, 0.08547226339578629, -0.017854180186986923, 0.03058786876499653, 0.060495343059301376, -0.015230463817715645, -0.06322644650936127, 0.07383410632610321, 0.06897479295730591, 0.028405973687767982, 0.03996932506561279, -0.12619061768054962, -0.0005962405120953918, 0.02177903801202774, 0.034483861178159714, 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0.017111703753471375, 0.09428240358829498, 0.03249414265155792, 0.04887842759490013, -6.063410751266929e-8, -0.011348182335495949, -0.035036351531744, -0.04029017686843872, -0.0669434517621994, 0.01605350151658058, -0.05105436593294144, -0.0038130793254822493, 0.044752344489097595, -0.011869579553604126, 0.0010117238853126764, 0.09432613849639893, 0.0023488951846957207, -0.04090110585093498, -0.07395609468221664, 0.06235198676586151, 0.006363394670188427, 0.018924545496702194, 0.11190354079008102, -0.017160458490252495, -0.06586888432502747, -0.030384689569473267, 0.10949989408254623, 0.07364025712013245, -0.04216330125927925, -0.07903499156236649, 0.04362843185663223, -0.008444567210972309, -0.07387237995862961, -0.030617758631706238, 0.028601786121726036, -0.0007663302239961922, 0.003253211500123143, 0.0315953828394413, -0.07873455435037613, 0.006945352535694838, 0.044047292321920395, -0.058674298226833344, -0.03230966627597809, 0.027005450800061226, 0.10210893303155899, 0.05933852866292, 0.000322566251270473, 0.0217839814722538, 0.10769732296466827, 0.12022484838962555, -0.009263443760573864, 0.03146320953965187, 0.03226190805435181, -0.0032081420067697763, -0.07820539176464081, 0.010663270950317383, 0.025090156123042107, -0.01604919694364071, -0.0025112756993621588, -0.08793340623378754, 0.011963814496994019, 0.04968341067433357, 0.11262602359056473, -0.0019601157400757074, -0.017279982566833496, 0.09509088099002838, 0.03212705999612808, 0.006802781950682402, 0.004724528174847364 ]
and\tthe\tAla\tallele\n\tthe\tvariant\tallele)\tand\tdietary\tfat\tintake.\tThose\twith\tthe\tPro/Pro\tgenotype\twho\talso\nhad\tthe\thighest\tdietary\tfat\tintake\thad\tsignificantly\thigher\tBMI\tvalues\tthan\tthose\twho\thad\tthe\tlowest\ndietary\tfat\tintake.\tThere\tdid\tnot\tappear\tto\tbe\ta\tgene–diet\tinteraction\twith\tthe\tAla\tallele\twith\trespect\nto\tBMI.\t\nRodrigues\tet\tal\t(2018)
[ -0.020200584083795547, -0.020429864525794983, 0.09266447275876999, -0.02112852968275547, -0.07788177579641342, -0.002948961453512311, 0.05936674401164055, -0.00913340225815773, -0.055561136454343796, 0.03990532457828522, 0.09585487097501755, -0.04598606005311012, -0.0061969514936208725, -0.033593714237213135, -0.023358505219221115, 0.00608437554910779, 0.018376098945736885, 0.009384805336594582, -0.06108219549059868, 0.004333801101893187, 0.005332375876605511, 0.020298674702644348, 0.08445760607719421, -0.026002012193202972, -0.04457380622625351, -0.05647081509232521, -0.008451932109892368, 0.029199881479144096, -0.03361935541033745, -0.016481049358844757, -0.09823648631572723, 0.06442207843065262, 0.027473004534840584, 0.01516043208539486, 0.03001258708536625, -0.04967295750975609, -0.05552035570144653, 0.023441096767783165, 0.07206364721059799, 0.03656329959630966, 0.0608353465795517, -0.16134895384311676, -0.027279775589704514, 0.027554498985409737, 0.05822395160794258, 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0.0579262375831604, 0.009095241315662861, 0.02930958941578865, 0.030823562294244766, -4.9470951779539973e-8, 0.021433746442198753, -0.06571245938539505, -0.022051388397812843, -0.006444074213504791, 0.03918128088116646, -0.026730861514806747, 0.0321301706135273, 0.008545616641640663, 0.06687510758638382, 0.007191848009824753, 0.059927888214588165, 0.07502125948667526, -0.052735693752765656, -0.0487920343875885, 0.03460261970758438, 0.018307263031601906, 0.032532960176467896, 0.1195487380027771, -0.02487974613904953, -0.08372535556554794, -0.03135691583156586, 0.07974202185869217, -0.005723147187381983, -0.03266167640686035, -0.051577936857938766, 0.029311414808034897, -0.005311490967869759, -0.07482302188873291, -0.04485183209180832, 0.006372510921210051, 0.062087833881378174, -0.027200795710086823, -0.018862951546907425, -0.05648745968937874, 0.001353596686385572, 0.032402731478214264, -0.027426699176430702, -0.04499299079179764, 0.023375246673822403, 0.11164252460002899, 0.04682262986898422, -0.015059205703437328, 0.027832191437482834, 0.06586739420890808, 0.08146560192108154, -0.04596056416630745, -0.008978109806776047, 0.04213336110115051, 0.03943805396556854, -0.0319397859275341, -0.05871587619185448, 0.0033217393793165684, 0.006971379742026329, -0.02766456827521324, -0.07578915357589722, -0.03259601071476936, 0.0721394270658493, 0.03942791372537613, 0.062395643442869186, 0.04455264285206795, 0.1323801875114441, 0.04822240024805069, 0.10175344347953796, 0.0032763357739895582 ]
to\tBMI.\t\nRodrigues\tet\tal\t(2018)\n\treported\ton\tseverely\tobese\tindividuals\tand\tfound\tthat\tthose\twith\tone\nor\tmore\n\tcopies\tof\tthe\tAla\tallele\thad\thigher\tBMI\tvalues\tand\thigher\tpolyunsaturated\tfat\tintake.\tIt\tis\nnot\tunusual\tto\tencounter\tthese\ttypes\tof\tinconsistencies\tas\tresearchers\tattempt\tto\tidentify\tSNPs\tthat
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