Accès ouvert déclaré 2022 article

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

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

66Citations signalées, ce qui n’est pas une note de qualité
328Institutions déclarées
36Pays d’affiliation déclarés

Rattachement africain : gb, us, cn, de, is, kr, jp, no, fi, pk, qa, Afrique du Sud, se, nl, Égypte, sg, dk, tw, es, it, ch, at, mx, ca, cz, au, in, kw, gr, hr, cl, sk, ph, lk, ir, sa. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.

Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis
Date Crossref
27/12/2022
Éditeur
Springer Science and Business Media LLC
Type
journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

  • Queen Mary University of London pays non établi dans la notice
    Université ou école supérieure
  • William Harvey Research Institute pays non établi dans la notice
    Structure de recherche
  • University of Michigan Department of Internal Medicine pays non établi dans la notice
    Université ou école supérieure
  • Boston University Department of Biostatistics pays non établi dans la notice
    Université ou école supérieure
  • Beijing Tongren Hospital pays non établi dans la notice
    Établissement de santé
  • Capital Medical University Beijing Institute of Ophthalmology pays non établi dans la notice
    Université ou école supérieure
  • University of Pennsylvania pays non établi dans la notice
    Université ou école supérieure
  • Pennsylvania State University Department of Statistics pays non établi dans la notice
    Université ou école supérieure
  • VA Palo Alto Health Care System pays non établi dans la notice
    Établissement de santé
  • Case Western Reserve University Department of Population and Quantitative Health Sciences pays non établi dans la notice
    Université ou école supérieure
  • Stanford University Department of Statistics pays non établi dans la notice
    Université ou école supérieure
  • Broad Institute Program in Medical and Population Genetics pays non établi dans la notice
    Organisation à but non lucratif

Queen Mary University of London, William Harvey Research Institute et Department of Internal Medicine — University of Michigan, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud, Égypte.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Genetic Associations and EpidemiologyDiabetes, Cardiovascular Risks, and LipoproteinsKruppel-like factors research
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