Genetic studies of plasma analytes identify novel potential biomarkers for several complex traits
Authors: Deming Yuetiva , Xia Jian , Cai Yefei , Lord Jenny , Del-Aguila Jorge L. , Fernandez Maria Victoria , Carrell David , Black Kathleen , Budde John , Ma ShengMei , Saef Benjamin , Howells Bill , Bertelsen Sarah , Bailey Matthew , Ridge Perry G. ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Hefti Franz , Fillit Howard , Zimmerman Earl A. , Celmins Dzintra , Brown Alice D. , Carrillo Maria , Fleisher Adam , Reeder Stephanie , Trncic Nadira , Burke Anna , Tariot Pierre , Reiman Eric M. , Chen Kewei , Sabbagh Marwan N. , Beiden Christine M. , Jacobson Sandra A. , Sirrel Sherye A. , Doody Rachelle S. , Villanueva-Meyer Javier , Chowdhury Munir , Rountree Susan , Dang Mimi , Kowall Neil , Killiany Ronald , Budson Andrew E. , Norbash Alexander , Johnson Patricia Lynn , Green Robert C. , Marshall Gad , Johnson Keith A. , Sperling Reisa A. , Snyder Peter , Salloway Stephen , Malloy Paul , Correia Stephen , Bernick Charles , Munic Donna , Stern Yaakov , Honig Lawrence S. , Bell Karen L. , Relkin Norman , Chaing Gloria , Ravdin Lisa , Paul Steven , Flashman Laura A. , Seltzer Marc , Hynes Mary L. , Santulli Robert B. , Bates Vernice , Capote Horacio , Rainka Michelle , Friedl Karl , Murali Doraiswamy P. , Petrella Jeffrey R. , Borges-Neto Salvador , James Olga , Wong Terence , Coleman Edward , Schwartz Adam , Cellar Janet S. , Levey Allan L. , Lah James J. , Behan Kelly , Scott Turner Raymond , Johnson Kathleen , Reynolds Brigid , Pearlson Godfrey D. , Blank Karen , Anderson Karen , Obisesan Thomas O. , Wolday Saba , Allard Joanne , Lerner Alan , Ogrocki Paula , Tatsuoka Curtis , Fatica Parianne , Farlow Martin R. , Saykin Andrew J. , Foroud Tatiana M. , Shen Li , Faber Kelly , Kim Sungeun , Nho Kwangsik , Marie Hake Ann , Matthews Brandy R. , Brosch Jared R. , Herring Scott , Hunt Cynthia , Albert Marilyn , Onyike Chiadi , D’Agostino Daniel , Kielb Stephanie , Graff-Radford Neill R , Parfitt Francine , Kendall Tracy , Johnson Heather , Petersen Ronald , Jack Clifford R. , Bernstein Matthew , Borowski Bret , Gunter Jeff , Senjem Matt , Vemuri Prashanthi , Jones David , Kantarci Kejal , Ward Chad , Mason Sara S. , Albers Colleen S. , Knopman David , Johnson Kris , Chertkow Howard , Hosein Chris , Mintzer Jacob , Spicer Kenneth , Bachman David , Grossman Hillel , Mitsis Effie , Pomara Nunzio , Hernando Raymundo , Sarrael Antero , Potter William , Buckholtz Neil , Hsiao John , Kittur Smita , Galvin James E. , Cerbone Brittany , Michel Christina A. , Pogorelec Dana M. , Rusinek Henry , de Leon Mony J , Glodzik Lidia , De Santi Susan , Johnson Nancy , Chuang-Kuo  , Kerwin Diana , Bonakdarpour Borna , Weintraub Sandra , Grafman Jordan , Lipowski Kristine , Mesulam Marek-Marsel , Scharre Douglas W. , Kataki Maria , Adeli Anahita , Kaye Jeffrey , Quinn Joseph , Silbert Lisa , Lind Betty , Carter Raina , Dolen Sara , Borrie Michael , Lee T-Y , Bartha Rob , Martinez Walter , Villena Teresa , Sadowsky Carl , Khachaturian Zaven , Ott Brian R. , Querfurth Henry , Tremont Geoffrey , Frank Richard , Fleischman Debra , Arfanakis Konstantinos , Shah Raj C. , deToledo-Morrell Leyla , Sorensen Greg , Finger Elizabeth , Pasternack Stephen , Rachinsky Irina , Drost Dick , Rogers John , Kertesz Andrew , Furst Ansgar J. , Chad Stevan , Yesavage Jerome , Taylor Joy L. , Lane Barton , Rosen Allyson , Tinklenberg Jared , Black Sandra , Stefanovic Bojana , Caldwell Curtis , Robin Hsiung Ging-Yuek , Mudge Benita , Assaly Michele , Fox Nick , Schultz Susan K. , Boles Ponto Laura L. , Shim Hyungsub , Ekstam Smith Karen , Burns Jeffrey M. , Swerdlow Russell H. , Brooks William M. , Marson Daniel , Griffith Randall , Clark David , Geldmacher David , Brockington John , Roberson Erik , Natelson Love Marissa , DeCarli Charles , Carmichael Owen , Olichney John , Maillard Pauline , Fletcher Evan , Nguyen Dana , Preda Andrian , Potkin Steven , Mulnard Ruth A. , Thai Gaby , McAdams-Ortiz Catherine , Landau Susan , Jagust William , Apostolova Liana , Tingus Kathleen , Woo Ellen , Silverman Daniel H.S. , Lu Po H. , Bartzokis George , Thompson Paul , Donohue Michael , Thomas Ronald G. , Walter Sarah , Gessert Devon , Brewer James , Vanderswag Helen , Sather Tamie , Jiminez Gus , Balasubramanian Archana B. , Mason Jennifer , Sim Iris , Aisen Paul , Davis Melissa , Morrison Rosemary , Harvey Danielle , Thal Lean , Beckett Laurel , Neylan Thomas , Finley Shannon , Weiner Michael W. , Hayes Jacqueline , Rosen Howard J. , Miller Bruce L. , Perry David , Massoglia Dino , Brawman-Mentzer Olga , Schuff Norbert , Smith Charles D. , Hardy Peter , Sinha Partha , Oates Elizabeth , Conrad Gary , Koeppe Robert A. , Lord Joanne L. , Heidebrink Judith L. , Arnold Steven E. , Karlawish Jason H. , Wolk David , Clark Christopher M. , Trojanowki John Q. , Shaw Leslie M. , Lee Virginia , Korecka Magdalena , Figurski Michal , Toga Arthur W. , Crawford Karen , Neu Scott , Schneider Lon S. , Pawluczyk Sonia , Beccera Mauricio , Teodoro Liberty , Spann Bryan M. , Womack Kyle , Mathews Dana , Quiceno Mary , Foster Norm , Montine Tom , Fruehling J. Jay , Harding Sandra , Johnson Sterling , Asthana Sanjay , Carlsson Cynthia M. , Petrie Eric C. , Peskind Elaine , Li Gail , Porsteinsson Anton P. , Goldstein Bonnie S. , Martin Kim , Makino Kelly M. , Ismail M. Saleem , Brand Connie , Smith Amanda , Ashok Raj Balebail , Fargher Kristin , Kuller Lew , Mathis Chet , Ann Oakley Mary , Lopez Oscar L. , Simpson Donna M. , Sink Kaycee M. , Gordineer Leslie , Williamson Jeff D. , Garg Pradeep , Watkins Franklin , Cairns Nigel J. , Raichle Marc , Morris John C. , Householder Erin , Taylor-Reinwald Lisa , Holtzman David , Ances Beau , Carroll Maria , Creech Mary L. , Franklin Erin , Mintun Mark A. , Schneider Stacy , Oliver Angela , Duara Ranjan , Varon Daniel , Greig Maria T. , Roberts Peggy , Varma Pradeep , MacAvoy Martha G. , Carson Richard E. , van Dyck Christopher H. , Davies Peter , Holtzman David , Morris John C. , Bales Kelly , Pickering Eve H. , Lee Jin-Moo , Heitsch Laura , Kauwe John , Goate Alison , Piccio Laura , Cruchaga Carlos 
Published: January 2016

Genome-wide association studies of 146 plasma protein levels in 818 individuals revealed 56 genome-wide significant associations (28 novel) with 47 analytes. Loci associated with plasma levels of 39 proteins tested have been previously associated with various complex traits such as heart disease, inflammatory bowel disease, Type 2 diabetes and multiple sclerosis. These data suggest that these plasma protein levels may constitute informative endophenotypes for these complex traits. We found three potential pleiotropic genes: ABO for plasma SELE and ACE levels, FUT2 for CA19-9 and CEA plasma levels and APOE for ApoE and CRP levels. We also found multiple independent signals in loci associated with plasma levels of ApoH, CA19-9, FetuinA, IL6r and LPa. Our study highlights the power of biological traits for genetic studies to identify genetic variants influencing clinically relevant traits, potential pleiotropic effects and complex disease associations in the same locus.