The power of genetic diversity in genome-wide association studies of lipids

Επιστημονική δημοσίευση - Άρθρο Περιοδικού uoadl:3033399 88 Αναγνώσεις

Μονάδα:
Ερευνητικό υλικό ΕΚΠΑ
Τίτλος:
The power of genetic diversity in genome-wide association studies of
lipids
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Increased blood lipid levels are heritable risk factors of
cardiovascular disease with varied prevalence worldwide owing to
different dietary patterns and medication use(1). Despite advances in
prevention and treatment, in particular through reducing low-density
lipoprotein cholesterol levels(2), heart disease remains the leading
cause of death worldwide(3). Genome-wideassociation studies (GWAS) of
blood lipid levels have led to important biological and clinical
insights, as well as new drug targets, for cardiovascular disease.
However, most previous GWAS(4-23) have been conducted in European
ancestry populations and may have missed genetic variants that
contribute to lipid-level variation in other ancestry groups. These
include differences in allele frequencies, effect sizes and
linkage-disequilibrium patterns(24). Here we conduct a multi-ancestry,
genome-wide genetic discovery meta-analysis of lipid levels in
approximately 1.65 million individuals, including 350,000 of
non-European ancestries. We quantify the gain in studying non-European
ancestries and provide evidence to support the expansion of recruitment
of additional ancestries, even with relatively small sample sizes. We
find that increasing diversity rather than studying additional
individuals of European ancestry results in substantial improvements in
fine-mapping functional variants and portability of polygenic prediction
(evaluated in approximately 295,000 individuals from 7 ancestry
groupings). Modest gains in the number of discovered loci and
ancestry-specific variants were also achieved. As GWAS expand emphasis
beyond the identification of genes and fundamental biology towards the
use of genetic variants for preventive and precision medicine(25), we
anticipate that increased diversity of participants will lead to more
accurate and equitable(26) application of polygenic scores in clinical
practice.
Έτος δημοσίευσης:
2021
Συγγραφείς:
Graham, Sarah E.
Clarke, Shoa L.
Wu, Kuan-Han H.
Kanoni,
Stavroula
Zajac, Greg J. M.
Ramdas, Shweta
Surakka, Ida and
Ntalla, Ioanna
Vedantam, Sailaja
Winkler, Thomas W.
Locke,
Adam E.
Marouli, Eirini
Hwang, Mi Yeong
Han, Sohee and
Narita, Akira
Choudhury, Ananyo
Bentley, Amy R.
Ekoru,
Kenneth
Verma, Anurag
Trivedi, Bhavi
Martin, Hilary C. and
Hunt, Karen A.
Hui, Qin
Klarin, Derek
Zhu, Xiang and
Thorleifsson, Gudmar
Helgadottir, Anna
Gudbjartsson, Daniel F.
and Holm, Hilma
Olafsson, Isleifur
Akiyama, Masato
Sakaue,
Saori
Terao, Chikashi
Kanai, Masahiro
Zhou, Wei and
Brumpton, Ben M.
Rasheed, Humaira
Ruotsalainen, Sanni E. and
Havulinna, Aki S.
Veturi, Yogasudha
Feng, QiPing
Rosenthal,
Elisabeth A.
Lingren, Todd
Pacheco, Jennifer Allen and
Pendergrass, Sarah A.
Haessler, Jeffrey
Giulianini, Franco and
Bradford, Yuki
Miller, Jason E.
Campbell, Archie
Lin, Kuang
and Millwood, Iona Y.
Hindy, George
Rasheed, Asif
Faul,
Jessica D.
Zhao, Wei
Weir, David R.
Turman, Constance and
Huang, Hongyan
Graff, Mariaelisa
Mahajan, Anubha
Brown,
Michael R.
Zhang, Weihua
Yu, Ketian
Schmidt, Ellen M. and
Pandit, Anita
Gustafsson, Stefan
Yin, Xianyong
Luan, Jian'an
and Zhao, Jing-Hua
Matsuda, Fumihiko
Jang, Hye-Mi
Yoon,
Kyungheon
Medina-Gomez, Carolina
Pitsillides, Achilleas and
Hottenga, Jouke Jan
Willemsen, Gonneke
Wood, Andrew R.
Ji,
Yingji
Gao, Zishan
Haworth, Simon
Mitchell, Ruth E. and
Chai, Jin Fang
Aadahl, Mette
Yao, Jie
Manichaikul, Ani and
Warren, Helen R.
Ramirez, Julia
Bork-Jensen, Jette
Karhus,
Line L.
Goel, Anuj
Sabater-Lleal, Maria
Noordam, Raymond and
Sidore, Carlo
Fiorillo, Edoardo
McDaid, Aaron F. and
Marques-Vidal, Pedro
Wielscher, Matthias
Trompet, Stella and
Sattar, Naveed
Mollehave, Line T.
Thuesen, Betina H.
Munz,
Matthias
Zeng, Lingyao
Huang, Jianfeng
Yang, Bin
Poveda,
Alaitz
Kurbasic, Azra
Lamina, Claudia
Forer, Lukas and
Scholz, Markus
Galesloot, Tessel E.
Bradfield, Jonathan P. and
Daw, E. Warwick
Zmuda, Joseph M.
Mitchell, Jonathan S. and
Fuchsberger, Christian
Christensen, Henry
Brody, Jennifer A. and
Feitosa, Mary F.
Wojczynski, Mary K.
Preuss, Michael and
Mangino, Massimo
Christofidou, Paraskevi
Verweij, Niek and
Benjamins, Jan W.
Engmann, Jorgen
Kember, Rachel L.
Slieker,
Roderick C.
Lo, Ken Sin
Zilhao, Nuno R.
Phuong Le and
Kleber, Marcus E.
Delgado, Graciela E.
Huo, Shaofeng
Ikeda,
Daisuke D.
Iha, Hiroyuki
Yang, Jian
Liu, Jun
Leonard,
Hampton L.
Marten, Jonathan
Schmidt, Borge
Arendt, Marina
and Smyth, Laura J.
Canadas-Garre, Marisa
Wang, Chaolong and
Nakatochi, Masahiro
Wong, Andrew
Hutri-Kahonen, Nina
Sim,
Xueling
Xia, Rui
Huerta-Chagoya, Alicia
Fernandez-Lopez,
Juan Carlos
Lyssenko, Valeriya
Ahmed, Meraj
Jackson, Anne U.
and Irvin, Marguerite R.
Oldmeadow, Christopher
Kim, Han-Na and
Ryu, Seungho
Timmers, Paul R. H. J.
Arbeeva, Liubov
Dorajoo,
Rajkumar
Lange, Leslie A.
Chai, Xiaoran
Prasad, Gauri and
Lores-Motta, Laura
Pauper, Marc
Long, Jirong
Li, Xiaohui and
Theusch, Elizabeth
Takeuchi, Fumihiko
Spracklen, Cassandra N.
and Loukola, Anu
Bollepalli, Sailalitha
Warner, Sophie C. and
Wang, Ya Xing
Wei, Wen B.
Nutile, Teresa
Ruggiero, Daniela
and Sung, Yun Ju
Hung, Yi-Jen
Chen, Shufeng
Liu, Fangchao
and Yang, Jingyun
Kentistou, Katherine A.
Gorski, Mathias and
Brumat, Marco
Meidtner, Karina
Bielak, Lawrence F.
Smith,
Jennifer A.
Hebbar, Prashantha
Farmaki, Aliki-Eleni
Hofer,
Edith
Lin, Maoxuan
Xue, Chao
Zhang, Jifeng
Concas, Maria
Pina
Vaccargiu, Simona
van der Most, Peter J.
Pitkanen,
Niina
Cade, Brian E.
Lee, Jiwon
van Der Laan, Sander W. and
Chitrala, Kumaraswamy Naidu
Weiss, Stefan
Zimmermann, Martina E.
and Lee, Jong Young
Choi, Hyeok Sun
Nethander, Maria and
Freitag-Wolf, Sandra
Southam, Lorraine
Rayner, Nigel W. and
Wang, Carol A.
Lin, Shih-Yi
Wang, Jun-Sing
Couture,
Christian
Lyytikainen, Leo-Pekka
Nikus, Kjell and
Cuellar-Partida, Gabriel
Vestergaard, Henrik
Hildalgo, Bertha
and Giannakopoulou, Olga
Cai, Qiuyin
Obura, Morgan O.
van
Setten, Jessica
Li, Xiaoyin
Schwander, Karen
Terzikhan,
Natalie
Shin, Jae Hun
Jackson, Rebecca D.
Reiner, Alexander
P.
Martin, Lisa Warsinger
Chen, Zhengming
Li, Liming and
Highland, Heather M.
Young, Kristin L.
Kawaguchi, Takahisa and
Thiery, Joachim
Bis, Joshua C.
Nadkarni, Girish N.
Launer,
Lenore J.
Li, Huaixing
Nalls, Mike A.
Raitakari, Olli T. and
Ichihara, Sahoko
Wild, Sarah H.
Nelson, Christopher P. and
Campbell, Harry
Jager, Susanne
Nabika, Toru
Al-Mulla, Fahd
and Niinikoski, Harri
Braund, Peter S.
Kolcic, Ivana
Kovacs,
Peter
Giardoglou, Tota
Katsuya, Tomohiro
Bhatti, Fatima and
de Kleijn, Dominique
de Borst, Gert J.
Kim, Eung Kweon and
Adams, Hieab H. H.
Ikram, M. Arfan
Zhu, Xiaofeng
Asselbergs,
Folkert W.
Kraaijeveld, Adriaan O.
Beulens, Joline W. J. and
Shu, Xiao-Ou
Rallidis, Loukianos S.
Pedersen, Oluf
Hansen,
Torben
Mitchell, Paul
Hewitt, Alex W.
Kahonen, Mika and
Perusse, Louis
Bouchard, Claude
Tonjes, Anke
Chen, Yii-Der
Ida
Pennell, Craig E.
Mori, Trevor A.
Lieb, Wolfgang and
Franke, Andre
Ohlsson, Claes
Mellstrom, Dan
Cho, Yoon Shin
and Lee, Hyejin
Yuan, Jian-Min
Koh, Woon-Puay
Rhee, Sang
Youl
Woo, Jeong-Taek
Heid, Iris M.
Stark, Klaus J. and
Volzke, Henry
Homuth, Georg
Evans, Michele K.
Zonderman,
Alan B.
Polasek, Ozren
Pasterkamp, Gerard
Hoefer, Imo E. and
Redline, Susan
Pahkala, Katja
Oldehinkel, Albertine J. and
Snieder, Harold
Biino, Ginevra
Schmidt, Reinhold
Schmidt,
Helena
Chen, Y. Eugene
Bandinelli, Stefania
Dedoussis,
George
Thanaraj, Thangavel Alphonse
Kardia, Sharon L. R. and
Kato, Norihiro
Schulze, Matthias B.
Girotto, Giorgia
Jung,
Bettina
Boger, Carsten A.
Joshi, Peter K.
Bennett, David A.
and De Jager, Philip L.
Lu, Xiangfeng
Mamakou, Vasiliki and
Brown, Morris
Caulfield, Mark J.
Munroe, Patricia B.
Guo,
Xiuqing
Ciullo, Marina
Jonas, Jost B.
Samani, Nilesh J. and
Kaprio, Jaakko
Pajukanta, Paivi
Adair, Linda S.
Bechayda,
Sonny Augustin
de Silva, H. Janaka
Wickremasinghe, Ananda R. and
Krauss, Ronald M.
Wu, Jer-Yuarn
Zheng, Wei
den Hollander, I,
Anneke
Bharadwaj, Dwaipayan
Correa, Adolfo
Wilson, James G.
and Lind, Lars
Heng, Chew-Kiat
Nelson, Amanda E.
Golightly,
Yvonne M.
Wilson, James F.
Penninx, Brenda
Kim, Hyung-Lae
and Attia, John
Scott, Rodney J.
Rao, D. C.
Arnett, Donna K.
and Walker, Mark
Koistinen, Heikki A.
Chandak, Giriraj R. and
Yajnik, Chittaranjan S.
Mercader, Josep M.
Tusie-Luna, Teresa
and Aguilar-Salinas, Carlos A.
Villalpando, Clicerio Gonzalez and
Orozco, Lorena
Fornage, Myriam
Tai, E. Shyong
van Dam, Rob
M.
Lehtimaki, Terho
Chaturvedi, Nish
Yokota, Mitsuhiro and
Liu, Jianjun
Reilly, Dermot F.
McKnight, Amy Jayne
Kee,
Frank
Jockel, Karl-Heinz
McCarthy, I, Mark
Palmer, Colin N.
A.
Vitart, Veronique
Hayward, Caroline
Simonsick, Eleanor
and van Duijn, Cornelia M.
Lu, Fan
Qu, Jia
Hishigaki,
Haretsugu
Lin, Xu
Marz, Winfried
Parra, Esteban J.
Cruz,
Miguel
Gudnason, Vilmundur
Tardif, Jean-Claude
Lettre,
Guillaume
`t Hart, Leen M.
Elders, Petra J. M.
Damrauer,
Scott M.
Kumari, Meena
Kivimaki, Mika
van der Harst, Pim and
Spector, Tim D.
Loos, Ruth J. F.
Province, Michael A.
Psaty,
Bruce M.
Brandslund, Ivan
Pramstaller, Peter P.
Christensen,
Kaare
Ripatti, Samuli
Widen, Elisabeth
Hakonarson, Hakon and
Grant, Struan F. A.
Kiemeney, Lambertus A. L. M.
de Graaf,
Jacqueline
Loeffler, Markus
Kronenberg, Florian
Gu, Dongfeng
and Erdmann, Jeanette
Schunkert, Heribert
Franks, Paul W. and
Linneberg, Allan
Jukema, J. Wouter
Khera, V, Amit
Mannikko,
Minna
Jarvelin, Marjo-Riitta
Kutalik, Zoltan
Cucca,
Francesco
Mook-Kanamori, Dennis O.
van Dijk, Ko Willems and
Watkins, Hugh
Strachan, David P.
Grarup, Niels
Sever, Peter
and Poulter, Neil
Rotter, I, Jerome
Dantoft, Thomas M. and
Karpe, Fredrik
Neville, Matt J.
Timpson, Nicholas J.
Cheng,
Ching-Yu
Wong, Tien-Yin
Khor, Chiea Chuen
Sabanayagam,
Charumathi
Peters, Annette
Gieger, Christian
Hattersley,
Andrew T.
Pedersen, Nancy L.
Magnusson, Patrik K. E. and
Boomsma, I, Dorret
de Geus, Eco J. C.
Cupples, L. Adrienne and
van Meurs, Joyce B. J.
Ghanbari, Mohsen
Rsen, Penny Gordon-La
and Huang, Wei
Kim, Young Jin
Tabara, Yasuharu
Wareham,
Nicholas J.
Langenberg, Claudia
Zeggini, Eleftheria and
Kuusisto, Johanna
Laakso, Markku
Ingelsson, Erik
Abecasis,
Goncalo
Chambers, John C.
Kooner, Jaspal S.
de Vries, Paul
S.
Morrison, Alanna C.
North, Kari E.
Daviglus, Martha and
Kraft, Peter
Martin, Nicholas G.
Whitfield, John B.
Abbas,
Shahid
Saleheen, Danish
Walters, Robin G.
Holmes, V, Michael
and Black, Corri
Smith, Blair H.
Justice, Anne E.
Baras,
Aris
Buring, Julie E.
Ridker, Paul M.
Chasman, I, Daniel and
Kooperberg, Charles
Wei, Wei-Qi
Jarvik, Gail P.
Namjou,
Bahram
Hayes, M. Geoffrey
Ritchie, Marylyn D.
Jousilahti,
Pekka
Salomaa, Veikko
Hveem, Kristian
Asvold, Bjorn Olav and
Kubo, Michiaki
Kamatani, Yoichiro
Okada, Yukinori
Murakami,
Yoshinori
Thorsteinsdottir, Unnur
Stefansson, Kari
Ho,
Yuk-Lam
Lynch, Julie A.
Rader, Daniel J.
Tsao, Philip S. and
Chang, Kyong-Mi
Cho, Kelly
O'Donnell, Christopher J. and
Gaziano, John M.
Wilson, Peter
Rotimi, Charles N. and
Hazelhurst, Scott
Ramsay, Michele
Trembath, Richard C.
van
Heel, David A.
Tamiya, Gen
Yamamoto, Masayuki
Kim, Bong-Jo
and Mohlke, Karen L.
Frayling, Timothy M.
Hirschhorn, Joel N.
and Kathiresan, Sekar
Boehnke, Michael
Natarajan, Pradeep and
Peloso, Gina M.
Brown, Christopher D.
Morris, Andrew P. and
Assimes, Themistocles L.
Deloukas, Panos
Sun, V, Yan
Willer,
Cristen J.
Περιοδικό:
Nature
Εκδότης:
NATURE PORTFOLIO
Τόμος:
600
Αριθμός / τεύχος:
7890
Σελίδες:
675+
Επίσημο URL (Εκδότης):
DOI:
10.1038/s41586-021-04064-3
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