Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases

Roselli, Carolina; Surakka, Ida; Olesen, Morten S.; Sveinbjornsson, Gardar; Marston, Nicholas A.; Choi, Seung Hoan; Holm, Hilma; Chaffin, Mark; Gudbjartsson, Daniel; Hill, Matthew C.; Aegisdottir, Hildur; Albert, Christine M.; Alonso, Alvaro; Anderson, Christopher D.; Arking, Dan E.; Arnar, David O.; Barnard, John; Benjamin, Emelia J.; Braunwald, Eugene; Brumpton, Ben; Campbell, Archie; Chami, Nathalie; Chasman, Daniel I.; Cho, Kelly; Choi, Eue-Keun; Christophersen, Ingrid E.; Chung, Mina K.; Conen, David; Crijns, Harry J.; Cutler, Michael J.; Czuba, Tomasz; Damrauer, Scott M.; Dichgans, Martin; Doerr, Marcus; Dudink, Elton; Duong, ThuyVy; Erikstrup, Christian; Esko, Tnu; Fatkin, Diane; Faul, Jessica D.; Ferreira, Manuel; Freitag, Daniel F.; Ganesh, Santhi K.; Gaziano, J. Michael; Geelhoed, Bastiaan; Ghouse, Jonas; Gieger, Christian; Giulianini, Franco; Graham, Sarah E.; Gudnason, Vilmundur; Guo, Xiuqing; Haggerty, Christopher; Hayward, Caroline; Heckbert, Susan R.; Hveem, Kristian; Ito, Kaoru; Johnson, Renee; Jukema, J. Wouter; Jurgens, Sean J.; Kaeaeb, Stefan; Kane, John P.; Kany, Shinwan; Kardia, Sharon L. R.; Kavousi, Maryam; Khurshid, Shaan; Kamanu, Frederick K.; Kirchhof, Paulus; Kleber, Marcus E.; Knight, Stacey; Komuro, Issei; Krieger, Jose E.; Launer, Lenore J.; Li, Dadong; Lin, Honghuang; Lin, Henry J.; Loos, Ruth J. F.; Lotta, Luca; Lubitz, Steven A.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Magnusson, Patrik K. E.; Malik, Rainer; Mantineo, Helene; Marcus, Gregory M.; Maerz, Winfried; McManus, David D.; Melander, Olle; Melloni, Giorgio E. M.; Meyre, Pascal B.; Miyazawa, Kazuo; Mohanty, Sanghamitra; Monfort, Laia M.; Mueller-Nurasyid, Martina; Nafissi, Navid A.; Natale, Andrea; Nazarian, Saman; Ostrowski, Sisse R.; Pak, Hui-Nam; Pang, Shichao; Pedersen, Ole B.; Pedersen, Nancy L.; Pereira, Alexandre C.; Pirruccello, James P.; Preuss, Michael; Psaty, Bruce M.; Pullinger, Clive R.; Rader, Daniel J.; Ramo, Joel T.; Ridker, Paul M.; Rienstra, Michiel; Risch, Lorenz; Roden, Dan M.; Rotter, Jerome I.; Sabatine, Marc S.; Schunkert, Heribert; Shah, Svati H.; Shim, Jaemin; Shoemaker, M. Benjamin; Simonson, Bridget; Sinner, Moritz F.; Smit, Roelof A. J.; Smith, Jennifer A.; Smith, Nicholas L.; Smith, J. Gustav; Soliman, Elsayed Z.; Sorensen, Erik; Sotoodehnia, Nona; Strbian, Daniel; Stricker, Bruno H.; Teder-Laving, Maris; Sun, Yan V.; Theriault, Sebastien; Thorolfsdottir, Rosa B.; Thorsteinsdottir, Unnur; Tveit, Arnljot; van der Harst, Pim; van Meurs, Joyce; Wang, Biqi; Weiss, Stefan; Wells, Quinn S.; Weng, Lu-Chen; Wilson, Peter W.; Xiao, Ling; Yang, Pil-Sung; Yao, Jie; Yoneda, Zachary T.; Zeller, Tanja; Zeng, Lingyao; Zhao, Wei; Zhou, Xiang; Zollner, Sebastian; Ruff, Christian T.; Bundgaard, Henning; Willer, Cristen; Stefansson, Kari; Ellinor, Patrick T.

doi:10.1038/s41588-024-02072-3

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Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases

Roselli, Carolina;
Surakka, Ida;
Olesen, Morten S.;
Sveinbjornsson, Gardar;
Marston, Nicholas A.;
... Shim, Jaemin;
외 150명

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초록

Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci. Furthermore, we assayed chromatin accessibility using assay for transposase-accessible chromatin with sequencing and histone H3 lysine 4 trimethylation in stem cell-derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility for our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known risk loci will facilitate a greater understanding of the pathways underlying AF.

키워드

Histone H3; Lysine; Article; Atrial Fibrillation; Cardiac Muscle; Cell Communication; Chromatin; Gene Locus; Genetic Risk Score; Genome-wide Association Study; Human; Meta Analysis; Muscle Contractility; Muscle Development; Single Nucleotide Polymorphism; Cardiac Muscle Cell; Female; Genetic Predisposition; Genetics; Male; Metabolism; Multifactorial Inheritance; Pathology; Risk Factor; Atrial Fibrillation; Chromatin; Female; Genetic Predisposition To Disease; Genome-wide Association Study; Humans; Male; Multifactorial Inheritance; Myocytes, Cardiac; Polymorphism, Single Nucleotide; Risk Factors; Lysine; Chromatin; VARIANTS; LOCI; MUTATION; COHORT; COMMON; ZFHX3

제목: Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases

저자: Roselli, Carolina; Surakka, Ida; Olesen, Morten S.; Sveinbjornsson, Gardar; Marston, Nicholas A.; Choi, Seung Hoan; Holm, Hilma; Chaffin, Mark; Gudbjartsson, Daniel; Hill, Matthew C.; Aegisdottir, Hildur; Albert, Christine M.; Alonso, Alvaro; Anderson, Christopher D.; Arking, Dan E.; Arnar, David O.; Barnard, John; Benjamin, Emelia J.; Braunwald, Eugene; Brumpton, Ben; Campbell, Archie; Chami, Nathalie; Chasman, Daniel I.; Cho, Kelly; Choi, Eue-Keun; Christophersen, Ingrid E.; Chung, Mina K.; Conen, David; Crijns, Harry J.; Cutler, Michael J.; Czuba, Tomasz; Damrauer, Scott M.; Dichgans, Martin; Doerr, Marcus; Dudink, Elton; Duong, ThuyVy; Erikstrup, Christian; Esko, Tnu; Fatkin, Diane; Faul, Jessica D.; Ferreira, Manuel; Freitag, Daniel F.; Ganesh, Santhi K.; Gaziano, J. Michael; Geelhoed, Bastiaan; Ghouse, Jonas; Gieger, Christian; Giulianini, Franco; Graham, Sarah E.; Gudnason, Vilmundur; Guo, Xiuqing; Haggerty, Christopher; Hayward, Caroline; Heckbert, Susan R.; Hveem, Kristian; Ito, Kaoru; Johnson, Renee; Jukema, J. Wouter; Jurgens, Sean J.; Kaeaeb, Stefan; Kane, John P.; Kany, Shinwan; Kardia, Sharon L. R.; Kavousi, Maryam; Khurshid, Shaan; Kamanu, Frederick K.; Kirchhof, Paulus; Kleber, Marcus E.; Knight, Stacey; Komuro, Issei; Krieger, Jose E.; Launer, Lenore J.; Li, Dadong; Lin, Honghuang; Lin, Henry J.; Loos, Ruth J. F.; Lotta, Luca; Lubitz, Steven A.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Magnusson, Patrik K. E.; Malik, Rainer; Mantineo, Helene; Marcus, Gregory M.; Maerz, Winfried; McManus, David D.; Melander, Olle; Melloni, Giorgio E. M.; Meyre, Pascal B.; Miyazawa, Kazuo; Mohanty, Sanghamitra; Monfort, Laia M.; Mueller-Nurasyid, Martina; Nafissi, Navid A.; Natale, Andrea; Nazarian, Saman; Ostrowski, Sisse R.; Pak, Hui-Nam; Pang, Shichao; Pedersen, Ole B.; Pedersen, Nancy L.; Pereira, Alexandre C.; Pirruccello, James P.; Preuss, Michael; Psaty, Bruce M.; Pullinger, Clive R.; Rader, Daniel J.; Ramo, Joel T.; Ridker, Paul M.; Rienstra, Michiel; Risch, Lorenz; Roden, Dan M.; Rotter, Jerome I.; Sabatine, Marc S.; Schunkert, Heribert; Shah, Svati H.; Shim, Jaemin; Shoemaker, M. Benjamin; Simonson, Bridget; Sinner, Moritz F.; Smit, Roelof A. J.; Smith, Jennifer A.; Smith, Nicholas L.; Smith, J. Gustav; Soliman, Elsayed Z.; Sorensen, Erik; Sotoodehnia, Nona; Strbian, Daniel; Stricker, Bruno H.; Teder-Laving, Maris; Sun, Yan V.; Theriault, Sebastien; Thorolfsdottir, Rosa B.; Thorsteinsdottir, Unnur; Tveit, Arnljot; van der Harst, Pim; van Meurs, Joyce; Wang, Biqi; Weiss, Stefan; Wells, Quinn S.; Weng, Lu-Chen; Wilson, Peter W.; Xiao, Ling; Yang, Pil-Sung; Yao, Jie; Yoneda, Zachary T.; Zeller, Tanja; Zeng, Lingyao; Zhao, Wei; Zhou, Xiang; Zollner, Sebastian; Ruff, Christian T.; Bundgaard, Henning; Willer, Cristen; Stefansson, Kari; Ellinor, Patrick T.

DOI: 10.1038/s41588-024-02072-3

발행일: 2025-03-06

유형: Article

저널명: Nature Genetics

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호: 3

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