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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- Title
- A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- Authors
- Ramdas, Shweta; Judd, Jonathan; Graham, Sarah E.; Kanoni, Stavroula; Wang, Yuxuan; Surakka, Ida; Wenz, Brandon; Clarke, Shoa L.; Chesi, Alessandra; Wells, Andrew; Bhatti, Konain Fatima; Vedantam, Sailaja; Winkler, Thomas W.; Locke, Adam E.; Marouli, Eirini; Zajac, Greg J. M.; Wu, Kuan-Han H.; Ntalla, Ioanna; Hui, Qin; Klarin, Derek; Hilliard, Austin T.; Wang, Zeyuan; Xue, Chao; Thorleifsson, Gudmar; Helgadottir, Anna; Gudbjartsson, Daniel F.; Holm, Hilma; Olafsson, Isleifur; Hwang, Mi Yeong; Han, Sohee; Akiyama, Masato; Sakaue, Saori; Terao, Chikashi; Kanai, Masahiro; Zhou, Wei; Brumpton, Ben M.; Rasheed, Humaira; Havulinna, Aki S.; Veturi, Yogasudha; Pacheco, Jennifer Allen; Rosenthal, Elisabeth A.; Lingren, Todd; Feng, QiPing; Kullo, Iftikhar J.; Narita, Akira; Takayama, Jun; Martin, Hilary C.; Hunt, Karen A.; Trivedi, Bhavi; Haessler, Jeffrey; Giulianini, Franco; Bradford, Yuki; Miller, Jason E.; Campbell, Archie; Lin, Kuang; Millwood, Iona Y.; Rasheed, Asif; Hindy, George; Faul, Jessica D.; Zhao, Wei; Weir, David R.; Turman, Constance; Huang, Hongyan; Graff, Mariaelisa; Choudhury, Ananyo; Sengupta, Dhriti; Mahajan, Anubha; Brown, Michael R.; Zhang, Weihua; Yu, Ketian; Schmidt, Ellen M.; Pandit, Anita; Gustafsson, Stefan; Yin, Xianyong; Luan, Jian'an; Zhao, Jing-Hua; Matsuda, Fumihiko; Jang, Hye-Mi; Yoon, Kyungheon; Medina-Gomez, Carolina; Pitsillides, Achilleas; Hottenga, Jouke Jan; Wood, Andrew R.; Ji, Yingji; Gao, Zishan; Haworth, Simon; Mitchell, Ruth E.; Chai, Jin Fang; Aadahl, Mette; Bjerregaard, Anne A.; Yao, Jie; Manichaikul, Ani; Lee, Wen-Jane; Hsiung, Chao Agnes; Warren, Helen R.; Ramirez, Julia; Bork-Jensen, Jette; Karhus, Line L.; Goel, Anuj; Sabater-Lleal, Maria; Noordam, Raymond; Mauro, Pala; Matteo, Floris; McDaid, Aaron F.; Marques-Vidal, Pedro; Wielscher, Matthias; Trompet, Stella; Sattar, Naveed; Mollehave, Line T.; Munz, Matthias; Zeng, Lingyao; Huang, Jianfeng; Yang, Bin; Poveda, Alaitz; Kurbasic, Azra; Schonherr, Sebastian; Forer, Lukas; Scholz, Markus; Galesloot, Tessel E.; Bradfield, Jonathan P.; Ruotsalainen, Sanni E.; Daw, E. Warwick; Zmuda, Joseph M.; Mitchell, Jonathan S.; Fuchsberger, Christian; Christensen, Henry; Brody, Jennifer A.; Le, Phuong; Feitosa, Mary F.; Wojczynski, Mary K.; Hemerich, Daiane; Preuss, Michael; Mangino, Massimo; Christofidou, Paraskevi; Verweij, Niek; Benjamins, Jan W.; Engmann, Jorgen; Noah, Tsao L.; Verma, Anurag; Slieker, Roderick C.; Lo, Ken Sin; Zilhao, Nuno R.; Kleber, Marcus E.; Delgado, Graciela E.; Huo, Shaofeng; Ikeda, Daisuke D.; Iha, Hiroyuki; Yang, Jian; Liu, Jun; Demirkan, Ayse; Leonard, Hampton L.; Marten, Jonathan; Emmel, Carina; Schmidt, Borge; Smyth, Laura J.; Canadas-Garre, Marisa; Wang, Chaolong; Nakatochi, Masahiro; Wong, Andrew; Hutri-Kahonen, Nina; Sim, Xueling; Xia, Rui; Huerta-Chagoya, Alicia; Fernandez-Lopez, Juan Carlos; Lyssenko, Valeriya; Nongmaithem, Suraj S.; Sankareswaran, Alagu; Irvin, Marguerite R.; Oldmeadow, Christopher; Kim, Han-Na; Ryu, Seungho; Timmers, Paul R. H. J.; Arbeeva, Liubov; Dorajoo, Rajkumar; Lange, Leslie A.; Prasad, Gauri; Lores-Motta, Laura; Pauper, Marc; Long, Jirong; Li, Xiaohui; Theusch, Elizabeth; Takeuchi, Fumihiko; Spracklen, Cassandra N.; Loukola, Anu; Bollepalli, Sailalitha; Warner, Sophie C.; Wang, Ya Xing; Wei, Wen B.; Nutile, Teresa; Ruggiero, Daniela; Sung, Yun Ju; Chen, Shufeng; Liu, Fangchao; Yang, Jingyun; Kentistou, Katherine A.; Banas, Bernhard; Morgan, Anna; Meidtner, Karina; Bielak, Lawrence F.; Smith, Jennifer A.; Hebbar, Prashantha; Farmaki, Aliki-Eleni; Hofer, Edith; Lin, Maoxuan; Concas, Maria Pina; Vaccargiu, Simona; van der Most, Peter J.; Pitkanen, Niina; Cade, Brian E.; van der Laan, Sander W.; Chitrala, Kumaraswamy Naidu; Weiss, Stefan; Bentley, Amy R.; Doumatey, Ayo P.; Adeyemo, Adebowale A.; Lee, Jong Young; Petersen, Eva R. B.; Nielsen, Aneta A.; Choi, Hyeok Sun; Nethander, Maria; Freitag-Wolf, Sandra; Southam, Lorraine; Rayner, Nigel W.; Wang, Carol A.; Lin, Shih-Yi; Wang, Jun-Sing; Couture, Christian; Lyytikainen, Leo-Pekka; Nikus, Kjell; Cuellar-Partida, Gabriel; Vestergaard, Henrik; Hidalgo, Bertha; Giannakopoulou, Olga; Cai, Qiuyin; Obura, Morgan O.; van Setten, Jessica; He, Karen Y.; Tang, Hua; Terzikhan, Natalie; Shin, Jae Hun; Jackson, Rebecca D.; Reiner, Alexander P.; Martin, Lisa Warsinger; Chen, Zhengming; Li, Liming; Kawaguchi, Takahisa; Thiery, Joachim; Bis, Joshua C.; Launer, Lenore J.; Li, Huaixing; Nalls, Mike A.; Raitakari, Olli T.; Ichihara, Sahoko; Wild, Sarah H.; Nelson, Christopher P.; Campbell, Harry; Jager, Susanne; Nabika, Toru; Al-Mulla, Fahd; Niinikoski, Harri; Braund, Peter S.; Kolcic, Ivana; Kovacs, Peter; Giardoglou, Tota; Katsuya, Tomohiro; de Kleijn, Dominique; de Borst, Gert J.; Kim, Eung Kweon; Adams, Hieab H. H.; Ikram, M. Arfan; Zhu, Xiaofeng; Asselbergs, Folkert W.; Kraaijeveld, Adriaan O.; Beulens, Joline W. J.; Shu, Xiao-Ou; Rallidis, Loukianos S.; Pedersen, Oluf; Hansen, Torben; Mitchell, Paul; Hewitt, Alex W.; Kahonen, Mika; Perusse, Louis; Bouchard, Claude; Tonjes, Anke; Chen, Yii-Der Ida; Pennell, Craig E.; Mori, Trevor A.; Lieb, Wolfgang; Franke, Andre; Ohlsson, Claes; Mellstrom, Dan; Cho, Yoon Shin; Lee, Hyejin; Yuan, Jian-Min; Koh, Woon-Puay; Rhee, Sang Youl; Woo, Jeong-Taek; Heid, Iris M.; Stark, Klaus J.; Zimmermann, Martina E.; Volzke, Henry; Homuth, Georg; Evans, Michele K.; Zonderman, Alan B.; Polasek, Ozren; Pasterkamp, Gerard; Hoefer, Imo E.; Redline, Susan; Pahkala, Katja; Oldehinkel, Albertine J.; Snieder, Harold; Biino, Ginevra; Schmidt, Reinhold; Schmidt, Helena; Bandinelli, Stefania; Dedoussis, George; Thanaraj, Thangavel Alphonse; Peyser, Patricia A.; Kato, Norihiro; Schulze, Matthias B.; Girotto, Giorgia; Boger, Carsten A.; Jung, Bettina; Joshi, Peter K.; Bennett, David A.; De Jager, Philip L.; Lu, Xiangfeng; Mamakou, Vasiliki; Brown, Morris; Caulfield, Mark J.; Munroe, Patricia B.; Guo, Xiuqing; Ciullo, Marina; Jonas, Jost B.; Samani, Nilesh J.; Kaprio, Jaakko; Pajukanta, Paivi; Tusie-Luna, Teresa; Aguilar-Salinas, Carlos A.; Adair, Linda S.; Bechayda, Sonny Augustin; de Silva, H. Janaka; Wickremasinghe, Ananda R.; Krauss, Ronald M.; Wu, Jer-Yuarn; Zheng, Wei; den Hollander, Anneke, I; Bharadwaj, Dwaipayan; Correa, Adolfo; Wilson, James G.; Lind, Lars; Heng, Chew-Kiat; Nelson, Amanda E.; Golightly, Yvonne M.; Wilson, James F.; Penninx, Brenda; Kim, Hyung-Lae; Attia, John; Scott, Rodney J.; Rao, D. C.; Arnett, Donna K.; Walker, Mark; Scott, Laura J.; Koistinen, Heikki A.; Chandak, Giriraj R.; Mercader, Josep M.; Villalpando, Clicerio Gonzalez; Orozco, Lorena; Fornage, Myriam; Tai, E. Shyong; van Dam, Rob M.; Lehtimaki, Terho; Chaturvedi, Nish; Yokota, Mitsuhiro; Liu, Jianjun; Reilly, Dermot F.; McKnight, Amy Jayne; Kee, Frank; Jockel, Karl-Heinz; McCarthy, Mark, I; Palmer, Colin N. A.; Vitart, Veronique; Hayward, Caroline; Simonsick, Eleanor; van Duijn, Cornelia M.; Jin, Zi-Bing; Lu, Fan; Hishigaki, Haretsugu; Lin, Xu; Marz, Winfried; Gudnason, Vilmundur; Tardif, Jean-Claude; Lettre, Guillaume; Hart, Leen M. T.; Elders, Petra J. M.; Rader, Daniel J.; Damrauer, Scott M.; Kumari, Meena; Kivimaki, Mika; van der Harst, Pim; Spector, Tim D.; Loos, Ruth J. F.; Province, Michael A.; Parra, Esteban J.; Cruz, Miguel; Psaty, Bruce M.; Brandslund, Ivan; Pramstaller, Peter P.; Rotimi, Charles N.; Christensen, Kaare; Ripatti, Samuli; Widen, Elisabeth; Hakonarson, Hakon; Grant, Struan F. A.; Kiemeney, Lambertus; de Graaf, Jacqueline; Loeffler, Markus; Kronenberg, Florian; Gu, Dongfeng; Erdmann, Jeanette; Schunkert, Heribert; Franks, Paul W.; Linneberg, Allan; Jukema, J. Wouter; Khera, Amit, V; Mannikko, Minna; Jarvelin, Marjo-Riitta; Kutalik, Zoltan; Francesco, Cucca; Mook-Kanamori, Dennis O.; van Dijk, Ko Willems; Watkins, Hugh; Strachan, David P.; Grarup, Niels; Sever, Peter; Poulter, Neil; Sheu, Wayne Huey-Herng; Rotter, Jerome, I; Dantoft, Thomas M.; Karpe, Fredrik; Neville, Matt J.; Timpson, Nicholas J.; Cheng, Ching-Yu; Wong, Tien-Yin; Khor, Chiea Chuen; Li, Hengtong; Sabanayagam, Charumathi; Peters, Annette; Gieger, Christian; Hattersley, Andrew T.; Pedersen, Nancy L.; Magnusson, Patrik K. E.; Boomsma, Dorret, I; de Geus, Eco J. C.; Cupples, L. Adrienne; van Meurs, Joyce B. J.; Ikram, Arfan; Ghanbari, Mohsen; Gordon-Larsen, Penny; Huang, Wei; Kim, Young Jin; Tabara, Yasuharu; Wareham, Nicholas J.; Langenberg, Claudia; Zeggini, Eleftheria; Tuomilehto, Jaakko; Kuusisto, Johanna; Laakso, Markku; Ingelsson, Erik; Abecasis, Goncalo; Chambers, John C.; Kooner, Jaspal S.; de Vries, Paul S.; Morrison, Alanna C.; Hazelhurst, Scott; Ramsay, Michele; North, Kari E.; Daviglus, Martha; Kraft, Peter; Martin, Nicholas G.; Whitfield, John B.; Abbas, Shahid; Saleheen, Danish; Walters, Robin G.; Holmes, Michael, V; Black, Corri; Smith, Blair H.; Baras, Aris; Justice, Anne E.; Buring, Julie E.; Ridker, Paul M.; Chasman, Daniel, I; Kooperberg, Charles; Tamiya, Gen; Yamamoto, Masayuki; van Heel, David A.; Trembath, Richard C.; Wei, Wei-Qi; Jarvik, Gail P.; Namjou, Bahram; Hayes, M. Geoffrey; Ritchie, Marylyn D.; Jousilahti, Pekka; Salomaa, Veikko; Hveem, Kristian; Asvold, Bjorn Olav; Kubo, Michiaki; Kamatani, Yoichiro; Okada, Yukinori; Murakami, Yoshinori; Kim, Bong-Jo; Thorsteinsdottir, Unnur; Stefansson, Kari; Zhang, Jifeng; Chen, Y. Eugene; Ho, Yuk-Lam; Lynch, Julie A.; Tsao, Philip S.; Chang, Kyong-Mi; Cho, Kelly; O'Donnell, Christopher J.; Gaziano, John M.; Wilson, Peter; Mohlke, Karen L.; Frayling, Timothy M.; Hirschhorn, Joel N.; Kathiresan, Sekar; Boehnke, Michael; Grant, Struan; Natarajan, Pradeep; Sun, Yan, V; Morris, Andrew P.; Deloukas, Panos; Peloso, Gina; Assimes, Themistocles L.; Willer, Cristen J.; Zhu, Xiang; Brown, Christopher D.|Million Vet Program; Global Lipids Genetics Consortium
- Ewha Authors
- 김형래; 이혜진
- SCOPUS Author ID
- 김형래; 이혜진
- Issue Date
- 2022
- Journal Title
- AMERICAN JOURNAL OF HUMAN GENETICS
- ISSN
- 0002-9297
1537-6605
- Citation
- AMERICAN JOURNAL OF HUMAN GENETICS vol. 109, no. 8, pp. 1366 - 1387
- Publisher
- CELL PRESS
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.1016/j.ajhg.2022.06.012
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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