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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

ABSTRACT: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

SUBMITTER: Schunkert H 

PROVIDER: S-EPMC3119261 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

Schunkert Heribert H   König Inke R IR   Kathiresan Sekar S   Reilly Muredach P MP   Assimes Themistocles L TL   Holm Hilma H   Preuss Michael M   Stewart Alexandre F R AF   Barbalic Maja M   Gieger Christian C   Absher Devin D   Aherrahrou Zouhair Z   Allayee Hooman H   Altshuler David D   Anand Sonia S SS   Andersen Karl K   Anderson Jeffrey L JL   Ardissino Diego D   Ball Stephen G SG   Balmforth Anthony J AJ   Barnes Timothy A TA   Becker Diane M DM   Becker Lewis C LC   Berger Klaus K   Bis Joshua C JC   Boekholdt S Matthijs SM   Boerwinkle Eric E   Braund Peter S PS   Brown Morris J MJ   Burnett Mary Susan MS   Buysschaert Ian I   Carlquist John F JF   Chen Li L   Cichon Sven S   Codd Veryan V   Davies Robert W RW   Dedoussis George G   Dehghan Abbas A   Demissie Serkalem S   Devaney Joseph M JM   Diemert Patrick P   Do Ron R   Doering Angela A   Eifert Sandra S   Mokhtari Nour Eddine El NE   Ellis Stephen G SG   Elosua Roberto R   Engert James C JC   Epstein Stephen E SE   de Faire Ulf U   Fischer Marcus M   Folsom Aaron R AR   Freyer Jennifer J   Gigante Bruna B   Girelli Domenico D   Gretarsdottir Solveig S   Gudnason Vilmundur V   Gulcher Jeffrey R JR   Halperin Eran E   Hammond Naomi N   Hazen Stanley L SL   Hofman Albert A   Horne Benjamin D BD   Illig Thomas T   Iribarren Carlos C   Jones Gregory T GT   Jukema J Wouter JW   Kaiser Michael A MA   Kaplan Lee M LM   Kastelein John J P JJ   Khaw Kay-Tee KT   Knowles Joshua W JW   Kolovou Genovefa G   Kong Augustine A   Laaksonen Reijo R   Lambrechts Diether D   Leander Karin K   Lettre Guillaume G   Li Mingyao M   Lieb Wolfgang W   Loley Christina C   Lotery Andrew J AJ   Mannucci Pier M PM   Maouche Seraya S   Martinelli Nicola N   McKeown Pascal P PP   Meisinger Christa C   Meitinger Thomas T   Melander Olle O   Merlini Pier Angelica PA   Mooser Vincent V   Morgan Thomas T   Mühleisen Thomas W TW   Muhlestein Joseph B JB   Münzel Thomas T   Musunuru Kiran K   Nahrstaedt Janja J   Nelson Christopher P CP   Nöthen Markus M MM   Olivieri Oliviero O   Patel Riyaz S RS   Patterson Chris C CC   Peters Annette A   Peyvandi Flora F   Qu Liming L   Quyyumi Arshed A AA   Rader Daniel J DJ   Rallidis Loukianos S LS   Rice Catherine C   Rosendaal Frits R FR   Rubin Diana D   Salomaa Veikko V   Sampietro M Lourdes ML   Sandhu Manj S MS   Schadt Eric E   Schäfer Arne A   Schillert Arne A   Schreiber Stefan S   Schrezenmeir Jürgen J   Schwartz Stephen M SM   Siscovick David S DS   Sivananthan Mohan M   Sivapalaratnam Suthesh S   Smith Albert A   Smith Tamara B TB   Snoep Jaapjan D JD   Soranzo Nicole N   Spertus John A JA   Stark Klaus K   Stirrups Kathy K   Stoll Monika M   Tang W H Wilson WH   Tennstedt Stephanie S   Thorgeirsson Gudmundur G   Thorleifsson Gudmar G   Tomaszewski Maciej M   Uitterlinden Andre G AG   van Rij Andre M AM   Voight Benjamin F BF   Wareham Nick J NJ   Wells George A GA   Wichmann H-Erich HE   Wild Philipp S PS   Willenborg Christina C   Witteman Jaqueline C M JC   Wright Benjamin J BJ   Ye Shu S   Zeller Tanja T   Ziegler Andreas A   Cambien Francois F   Goodall Alison H AH   Cupples L Adrienne LA   Quertermous Thomas T   März Winfried W   Hengstenberg Christian C   Blankenberg Stefan S   Ouwehand Willem H WH   Hall Alistair S AS   Deloukas Panos P   Thompson John R JR   Stefansson Kari K   Roberts Robert R   Thorsteinsdottir Unnur U   O'Donnell Christopher J CJ   McPherson Ruth R   Erdmann Jeanette J   Samani Nilesh J NJ  

Nature genetics 20110306 4

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were  ...[more]

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