Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Joanne M Murabito, Charles C White, Maryam Kavousi, Hong Yan Sun, Mary F Feitosa, Vijay Nambi, Claudia Lamina, Arne Schillert, Stefan Coassin, Joshua C Bis, Linda Broer, Dana C Crawford, Nora Franceschini, Ruth Frikke-Schmidt, Margot Haun, Suzanne Holewijn, Jennifer E Huffman, Shih-Jen Hwang, Stefan Kiechl, Barbara KolleritsMay E Montasser, Ilja M Nolte, Megan E Rudock, Andrea Senft, Alexander Teumer, Pim van der Harst, Veronique Vitart, Lindsay L Waite, Andrew R Wood, Christina L Wassel, Devin M Absher, Matthew A Allison, Najaf Amin, Alice Arnold, Folkert W Asselbergs, Yurii Aulchenko, Stefania Bandinelli, Maja Barbalic, Mladen Boban, Kristin Brown-Gentry, David J Couper, Michael H Criqui, Abbas Dehghan, Martin den Heijer, Benjamin Dieplinger, Jingzhong Ding, Marcus Dörr, Christine Espinola-Klein, Stephan B Felix, Luigi Ferrucci, Aaron R Folsom, Gustav Fraedrich, Quince Gibson, Robert Goodloe, Grgo Gunjaca, Meinhard Haltmayer, Gerardo Heiss, Albert Hofman, Arne Kieback, Lambertus A Kiemeney, Ivana Kolcic, Iftikhar J Kullo, Stephen B Kritchevsky, Karl J Lackner, Xiaohui Li, Wolfgang Lieb, Kurt Lohman, Christa Meisinger, David Melzer, Emile R Mohler, Ivana Mudnic, Thomas Mueller, Gerjan Navis, Friedrich Oberhollenzer, Jeffrey W Olin, Jeff O'Connell, Christopher J O'Donnell, Walter Palmas, Brenda W Penninx, Astrid Petersmann, Ozren Polasek, Bruce M Psaty, Barbara Rantner, Ken Rice, Fernando Rivadeneira, Jerome I Rotter, Adrie Seldenrijk, Marietta Stadler, Monika Summerer, Toshiko Tanaka, Anne Tybjærg-Hansen, Andre G Uitterlinden, Wiek H van Gilst, Sita H Vermeulen, Sarah H Wild, Philipp S Wild, Johann Willeit, Tanja Zeller, Tatijana Zemunik, Lina Zgaga, Themistocles L Assimes, Stefan Blankenberg, Eric Boerwinkle, Harry Campbell, John P Cooke, Jaqueline de Graaf, David Herrington, Sharon L R Kardia, Braxton D Mitchell, Anna Murray, Thomas Münzel, Anne Newman, Ben A Oostra, Igor Rudan, Alan R Shuldiner, Harold Snieder, Cornelia M van Duijn, Uwe Völker, Alan F Wright, H-Erich Wichmann, James Wilson, Jacqueline C M Witteman, Yongmei Liu, Caroline Hayward, Ingrid B Borecki, Andreas Ziegler, Kari E North, L Adrienne Cupples, Florian Kronenberg

91 Citationer (Scopus)

Abstract

BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. METHODS AND RESULTS: -Continuous ABI and PAD (ABI≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β= -0.006, p=2.46x10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI: DAB21P (rs13290547, p=3.6x10(-5)); CYBA (rs3794624, p=6.3x10(-5)); and rs1122608 (LDLR, p=0.0026). CONCLUSIONS: -GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI.
OriginalsprogEngelsk
TidsskriftCirculation: Cardiovascular Genetics
Vol/bind5
Sider (fra-til)100-112
ISSN1942-325X
DOI
StatusUdgivet - 2012

Fingeraftryk

Dyk ned i forskningsemnerne om 'Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies'. Sammen danner de et unikt fingeraftryk.

Citationsformater