A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
Creators: name: Vitart, Veronique
name: Weiss, Stefan
name: Erdmann, Jeanette
name: Hveem, Kristian
name: Kronenberg, Florian
name: Lee, Wen-Jane
name: Martin, Hilary C.
name: Feng, QiPing
name: Stark, Klaus J.
name: Kraft, Peter
name: Noordam, Raymond
name: Giulianini, Franco
name: Vedantam, Sailaja
name: van der Most, Peter J.
name: Peyser, Patricia A.
name: Braund, Peter S.
name: Magnusson, Patrik K.E.
name: Chandak, Giriraj R.
name: Launer, Lenore J.
name: Namjou, Bahram
name: Hakonarson, Hakon
name: Schunkert, Heribert
name: Hindy, George
name: Takayama, Jun
name: Daviglus, Martha
name: Heid, Iris M.
name: Abbas, Shahid
name: Jin, Zi-Bing
name: Bradfield, Jonathan P.
name: Arbeeva, Liubov
name: Mauro, Pala
name: Delgado, Graciela E.
name: Hwang, Mi Yeong
name: Mamakou, Vasiliki
name: Yamamoto, Masayuki
name: Cuellar-Partida, Gabriel
name: Freitag-Wolf, Sandra
name: Lorés-Motta, Laura
name: Kato, Norihiro
name: Penninx, Brenda
name: de Graaf, Jacqueline
name: Faul, Jessica D.
name: Mercader, Josep M.
name: Leonard, Hampton L.
name: Natarajan, Pradeep
name: Strachan, David P.
name: Wood, Andrew R.
name: Pacheco, Jennifer Allen
name: van Duijn, Cornelia M.
name: Sever, Peter
name: Whitfield, John B.
name: de Borst, Gert J.
name: Nalls, Mike A.
name: Kentistou, Katherine A.
name: Hofer, Edith
name: Dorajoo, Rajkumar
name: Zimmermann, Martina E.
name: Buring, Julie E.
name: Thiery, Joachim
name: Wang, Carol A.
name: Parra, Esteban J.
name: Scott, Rodney J.
name: Lieb, Wolfgang
name: Kathiresan, Sekar
name: Kiemeney, Lambertus
name: Kullo, Iftikhar J.
name: Vestergaard, Henrik
name: Poulter, Neil
name: Marten, Jonathan
name: Chang, Kyong-Mi
name: Boomsma, Dorret I.
name: Pajukanta, Päivi
name: Smyth, Laura J.
name: Simonsick, Eleanor
name: Holmes, Michael V.
name: Matsuda, Fumihiko
name: Gustafsson, Stefan
name: Choudhury, Ananyo
name: Banas, Bernhard
name: Koh, Woon-Puay
name: Li, Huaixing
name: Lin, Maoxuan
name: Neville, Matt J.
name: Reiner, Alexander P.
name: Chen, Shufeng
name: Evans, Michele K.
name: Golightly, Yvonne M.
name: Mellström, Dan
name: Judd, Jonathan
name: Chambers, John C.
name: Zhu, Xiaofeng
name: Kurbasic, Azra
name: Bollepalli, Sailalitha
name: Brown, Michael R.
name: Wang, Zeyuan
name: Nongmaithem, Suraj S.
name: Schulze, Matthias B.
name: de Geus, Eco J.C.
name: Zhao, Jing-Hua
name: Han, Sohee
name: Timpson, Nicholas J.
name: Graff, Mariaelisa
name: Willer, Cristen J.
name: Baras, Aris
name: Kim, Hyung-Lae
name: Shu, Xiao-Ou
name: Gao, Zishan
name: Beulens, Joline W.J.
name: Yokota, Mitsuhiro
name: Hsiung, Chao Agnes
name: Okada, Yukinori
name: Kutalik, Zoltan
name: Brody, Jennifer A.
name: Gieger, Christian
name: Schmidt, Ellen M.
name: Hilliard, Austin T.
name: Oldmeadow, Christopher
name: Jung, Bettina
name: Ikram, Arfan
name: Tai, E. Shyong
name: Bharadwaj, Dwaipayan
name: Hansen, Torben
name: Linneberg, Allan
name: Chaturvedi, Nish
name: Thorsteinsdottir, Unnur
name: Kamatani, Yoichiro
name: van Dijk, Ko Willems
name: Christensen, Henry
name: Fernandez-Lopez, Juan Carlos
name: Sung, Yun Ju
name: Peters, Annette
name: Francesco, Cucca
name: Ramdas, Shweta
name: van Meurs, Joyce B.J.
name: Obura, Morgan O.
name: Pandit, Anita
name: Ramirez, Julia
name: Giardoglou, Tota
name: Correa, Adolfo
name: Asselbergs, Folkert W.
name: Southam, Lorraine
name: Reilly, Dermot F.
name: Schmidt, Reinhold
name: Kim, Bong-Jo
name: Ritchie, Marylyn D.
name: Girotto, Giorgia
name: Hui, Qin
name: Miller, Jason E.
name: Mori, Trevor A.
name: Yang, Jingyun
name: Jukema, J. Wouter
name: Watkins, Hugh
name: Li, Xiaohui
name: de Vries, Paul S.
name: Justice, Anne E.
name: Christofidou, Paraskevi
name: Petersen, Eva R.B.
name: Gudbjartsson, Daniel F.
name: Heng, Chew-Kiat
name: Tsao, Philip S.
name: Bhatti, Konain Fatima
name: Dedoussis, George
name: Jarvelin, Marjo-Riitta
name: McKnight, Amy Jayne
name: Hoefer, Imo E.
name: Hidalgo, Bertha
name: Ikeda, Daisuke D.
name: Jackson, Rebecca D.
name: Sattar, Naveed
name: Ramsay, Michèle
name: Kuusisto, Johanna
name: Aadahl, Mette
name: Chen, Y. Eugene
name: Ohlsson, Claes
name: Meidtner, Karina
name: Kolcic, Ivana
name: Stefansson, Kari
name: Zmuda, Joseph M.
name: Snieder, Harold
name: Männikkö, Minna
name: Ruotsalainen, Sanni E.
name: Mahajan, Anubha
name: Zhang, Weihua
name: Morris, Andrew P.
name: Kooperberg, Charles
name: Huo, Shaofeng
name: Hazelhurst, Scott
name: Tuomilehto, Jaakko
name: Lee, Hyejin
name: Zhu, Xiang
name: Bjerregaard, Anne A.
name: Krauss, Ronald M.
name: Li, Liming
name: Ichihara, Sahoko
name: Thorleifsson, Gudmar
name: Oldehinkel, Albertine J.
name: Kumari, Meena
name: Pérusse, Louis
name: Wong, Tien-Yin
name: Sun, Yan V.
name: Psaty, Bruce M.
name: Verma, Anurag
name: Daw, E. Warwick
name: Lee, Jong Young
name: Lind, Lars
name: Aguilar-Salinas, Carlos A.
name: Yoon, Kyungheon
name: Niinikoski, Harri
name: Munroe, Patricia B.
name: van der Laan, Sander W.
name: Mitchell, Ruth E.
name: McCarthy, Mark I.
name: Hollander, Anneke I. den
name: Bis, Joshua C.
name: Dantoft, Thomas M.
name: Munz, Matthias
name: Kleber, Marcus E.
name: Spector, Tim D.
name: Sabanayagam, Charumathi
name: Peloso, Gina
name: Kivimaki, Mika
name: Concas, Maria Pina
name: de Silva, H. Janaka
name: Brandslund, Ivan
name: Hottenga, Jouke Jan
name: Sakaue, Saori
name: Hattersley, Andrew T.
name: Jonas, Jost B.
name: Prasad, Gauri
name: Olafsson, Isleifur
name: Palmer, Colin N.A.
name: Wilson, James F.
name: Wong, Andrew
name: Martin, Nicholas G.
name: Scholz, Markus
name: Grant, Struan
name: Jäger, Susanne
name: Wells, Andrew
name: Loos, Ruth J.F.
name: Engmann, Jorgen
name: Assimes, Themistocles L.
name: Gordon-Larsen, Penny
name: Lange, Leslie A.
name: Pedersen, Nancy L.
name: Wu, Kuan-Han H.
name: Chesi, Alessandra
name: Bandinelli, Stefania
name: Yang, Bin
name: Kaprio, Jaakko
name: Galesloot, Tessel E.
name: Joshi, Peter K.
name: Hayward, Caroline
name: Manichaikul, Ani
name: Guo, Xiuqing
name: Forer, Lukas
name: Jang, Hye-Mi
name: Kim, Han-Na
name: Choi, Hyeok Sun
name: Martin, Lisa Warsinger
name: Loukola, Anu
name: Lingren, Todd
name: Ikram, M. Arfan
name: Møllehave, Line T.
name: Marouli, Eirini
name: Zhang, Jifeng
name: Demirkan, Ayşe
name: Rasheed, Humaira
name: Frayling, Timothy M.
name: Nethander, Maria
name: Poveda, Alaitz
name: de Kleijn, Dominique
name: Program, Million Veterans
name: Samani, Nilesh J.
name: Lu, Xiangfeng
name: Veturi, Yogasudha
name: Lyssenko, Valeriya
name: Ingelsson, Erik
name: Huang, Hongyan
name: Smith, Jennifer A.
name: Ryu, Seungho
name: McDaid, Aaron F.
name: Kraaijeveld, Adriaan O.
name: Huang, Jianfeng
name: Province, Michael A.
name: Turman, Constance
name: Chen, Zhengming
name: Attia, John
name: Rayner, Nigel W.
name: Sabater-Lleal, Maria
name: Mohlke, Karen L.
name: Hirschhorn, Joel N.
name: Brumpton, Ben M.
name: Lin, Xu
name: Irvin, Marguerite R.
name: Damrauer, Scott M.
name: Medina-Gomez, Carolina
name: Hebbar, Prashantha
name: Rasheed, Asif
name: Pahkala, Katja
name: Locke, Adam E.
name: Feitosa, Mary F.
name: Cupples, L. Adrienne
name: Tardif, Jean-Claude
name: Zhou, Wei
name: Rotimi, Charles N.
name: Xia, Rui
name: Couture, Christian
name: Walker, Mark
name: Clarke, Shoa L.
name: Katsuya, Tomohiro
name: Murakami, Yoshinori
name: Gaziano, John M.
name: Havulinna, Aki S.
name: Liu, Jianjun
name: Zajac, Greg J.M.
name: Hayes, M. Geoffrey
name: Widén, Elisabeth
name: Ntalla, Ioanna
name: Lin, Kuang
name: Mangino, Massimo
name: Kim, Young Jin
name: Wu, Jer-Yuarn
name: Hunt, Karen A.
name: Nelson, Amanda E.
name: O'Donnell, Christopher J.
name: Pasterkamp, Gerard
name: Mook-Kanamori, Dennis O.
name: Shin, Jae Hun
name: Chen, Yii-Der Ida
name: Huerta-Chagoya, Alicia
name: Ruggiero, Daniela
name: Homuth, Georg
name: Gu, Dongfeng
name: Bentley, Amy R.
name: Lettre, Guillaume
name: Preuss, Michael
name: Tabara, Yasuharu
name: Khera, Amit V.
name: Adams, Hieab H.H.
name: De Jager, Philip L.
name: Luan, Jian’an
name: Sengupta, Dhriti
name: Jarvik, Gail P.
name: Polasek, Ozren
name: Pennell, Craig E.
name: Liu, Fangchao
name: Koistinen, Heikki A.
name: Franks, Paul W.
name: Zeggini, Eleftheria
name: Wickremasinghe, Ananda R.
name: Marques-Vidal, Pedro
name: Kubo, Michiaki
name: Pramstaller, Peter P.
name: Hemerich, Daiane
name: Timmers, Paul R.H.J.
name: Doumatey, Ayo P.
name: Xue, Chao
name: Hart, Leen M. t
name: Kim, Eung Kweon
name: Brown, Morris
name: Giannakopoulou, Olga
name: Kähönen, Mika
name: Cheng, Ching-Yu
name: Cruz, Miguel
name: Pedersen, Oluf
name: Haworth, Simon
name: Noah, Tsao L.
name: Villalpando, Clicerio Gonzalez
name: Zhao, Wei
name: Haessler, Jeffrey
name: Grarup, Niels
name: Caulfield, Mark J.
name: Zheng, Wei
name: Farmaki, Aliki-Eleni
name: Chai, Jin Fang
name: Kovacs, Peter
name: Saleheen, Danish
name: Trompet, Stella
name: Rotter, Jerome I.
name: Trembath, Richard C.
name: Hewitt, Alex W.
name: Tönjes, Anke
name: Li, Hengtong
name: Cai, Qiuyin
name: Grant, Struan F.A.
name: Nakatochi, Masahiro
name: Akiyama, Masato
name: Ciullo, Marina
name: Lu, Fan
name: Morgan, Anna
name: Wareham, Nicholas J.
name: Salomaa, Veikko
name: Chasman, Daniel I.
name: Walters, Robin G.
name: Wielscher, Matthias
name: van Heel, David A.
name: Benjamins, Jan W.
name: Bouchard, Claude
name: Khor, Chiea Chuen
name: Ghanbari, Mohsen
name: Adeyemo, Adebowale A.
name: Loeffler, Markus
name: Wilson, James G.
name: Helgadottir, Anna
name: Tusié-Luna, Teresa
name: Ji, Yingji
name: Wei, Wen B.
name: Orozco, Lorena
name: Wang, Chaolong
name: Raitakari, Olli T.
name: Jousilahti, Pekka
name: Ridker, Paul M.
name: Rallidis, Loukianos S.
name: Smith, Blair H.
name: van der Harst, Pim
name: Deloukas, Panos
name: Trivedi, Bhavi
name: Völzke, Henry
name: Nelson, Christopher P.
name: Cade, Brian E.
name: Nielsen, Aneta A.
name: Warren, Helen R.
name: Pitsillides, Achilleas
name: Verweij, Niek
name: Rosenthal, Elisabeth A.
name: Franke, Andre
name: Narita, Akira
name: Bechayda, Sonny Augustin
name: Sheu, Wayne Huey-Herng
name: Kee, Frank
name: Cañadas-Garre, Marisa
name: van Dam, Rob M.
name: Wang, Ya Xing
name: Terzikhan, Natalie
name: Nutile, Teresa
name: Fornage, Myriam
name: Black, Corri
name: Zilhao, Nuno R.
name: Rhee, Sang Youl
name: Pitkänen, Niina
name: Nabika, Toru
name: Zonderman, Alan B.
name: Boehnke, Michael
name: Kooner, Jaspal S.
name: Laakso, Markku
name: Campbell, Harry
name: Langenberg, Claudia
name: Cho, Yoon Shin
name: Wenz, Brandon
name: Weir, David R.
name: van Setten, Jessica
name: Warner, Sophie C.
name: Tang, Hua
name: Lehtimäki, Terho
name: Wilson, Peter
name: Schönherr, Sebastian
name: Al-Mulla, Fahd
name: Millwood, Iona Y.
name: Yao, Jie
name: Spracklen, Cassandra N.
name: Wang, Yuxuan
name: Schmidt, Börge
name: Redline, Susan
name: Theusch, Elizabeth
name: Le, Phuong
name: Yuan, Jian-Min
name: He, Karen Y.
name: Morrison, Alanna C.
name: Kanai, Masahiro
name: Elders, Petra J.M.
name: Mitchell, Paul
name: Slieker, Roderick C.
name: Consortium, Global Lipids Genetics
name: Adair, Linda S.
name: Abecasis, Goncalo
name: Matteo, Floris
name: Liu, Jun
name: Zeng, Lingyao
name: Graham, Sarah E.
name: Emmel, Carina
name: Surakka, Ida
name: Takeuchi, Fumihiko
name: Woo, Jeong-Taek
name: Goel, Anuj
name: März, Winfried
name: Ho, Yuk-Lam
name: Bork-Jensen, Jette
name: Hishigaki, Haretsugu
name: Lo, Ken Sin
name: Rader, Daniel J.
name: Terao, Chikashi
name: Mitchell, Jonathan S.
name: Yu, Ketian
name: Hutri-Kähönen, Nina
name: Yang, Jian
name: Lin, Shih-Yi
name: Long, Jirong
name: Rao, D.C.
name: Schmidt, Helena
name: Kanoni, Stavroula
name: Campbell, Archie
name: Klarin, Derek
name: Tamiya, 
name: Böger, Carsten A.
name: Cho, Kelly
name: Kawaguchi, Takahisa
name: Wild, Sarah H.
name: Gudnason, Vilmundur
name: Lynch, Julie A.
name: Holm, Hilma
name: Christensen, Kaare
name: Sim, Xueling
name: Karpe, Fredrik
name: Arnett, Donna K.
name: Lyytikäinen, Leo-Pekka
name: Pauper, Marc
name: Fuchsberger, Christian
name: Winkler, Thomas W.
name: Thanaraj, Thangavel Alphonse
name: Wang, Jun-Sing
name: Bennett, David A.
name: Iha, Hiroyuki
name: Yin, Xianyong
name: Chitrala, Kumaraswamy Naidu
name: Jöckel, Karl-Heinz
name: North, Kari E.
name: Scott, Laura J.
name: Wei, Wei-Qi
name: Bielak, Lawrence F.
name: Åsvold, Bjørn Olav
name: Brown, Christopher D.
name: Biino, Ginevra
name: Ripatti, Samuli
name: Kårhus, Line L.
name: Bradford, Yuki
name: Wojczynski, Mary K.
name: Nikus, Kjell
name: Sankareswaran, Alagu
name: Vaccargiu, Simona
name: Huang, Wei
Publisher: name: Elsevier
Year: 2022

description: <p>A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.</p>