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

JM Murabito, CC White, Maryam Kavousi, YV Sun, MF Feitosa, V Nambi, C Lamina, A Schillert, S Coassin, JC Bis, Linda Broer, DC Crawford, N Franceschini, R Frikke-Schmidt, M Haun, S Holewijn, JE Huffman, SJ Hwang, S Kiechl, B KolleritsME Montasser, IM (Ilja) Nolte, ME Rudock, A Senft, A Teumer, P van der Harst, V Vitart, LL Waite, AR Wood, CL Wassel, DM Absher, MA Allison, Najaf Amin, A Arnold, FW Asselbergs, Yuriy Aulchenko, S Bandinelli, M Barbalic, M Boban, K Brown-Gentry, DJ Couper, MH Criqui, Abbas Dehghan, Mariska Heijer, B Dieplinger, JZ (Jing Zhong) Ding, M Dorr, C Espinola-Klein, SB Felix, L Ferrucci, AR Folsom, G Fraedrich, Q Gibson, R Goodloe, G Gunjaca, M Haltmayer, G Heiss, Bert Hofman, A Kieback, LA Kiemeney, I Kolcic, IJ Kullo, SB Kritchevsky, KJ Lackner, XH Li, WG Lieb, K Lohman, C Meisinger, D Melzer, ER Mohler, I Mudnic, T Mueller, G Navis, F Oberhollenzer, JW Olin, J O'Connell, CJ O'Donnell, W Palmas, BW Penninx, A Petersmann, O Polasek, BM Psaty, B Rantner, K Rice, Fernando Rivadeneira, JI Rotter, A Seldenrijk, M Stadler, M Summerer, T Tanaka, A Tybjaerg-Hansen, André Uitterlinden, WH van Gilst, SH Vermeulen, SH Wild, PS Wild, J Willeit, T Zeller, T Zemunik, L Zgaga, TL Assimes, S Blankenberg, E Boerwinkle, H Campbell, JP Cooke, J van der Graaf, D Herrington, SLR Kardia, BD Mitchell, A Murray, T Munzel, AB Newman, Ben Oostra, I Rudan, AR Shuldiner, H Snieder, Cornelia Duijn, U Volker, AF Wright, HE Wichmann, JF Wilson, JCM Witteman, YM Liu, C Hayward, IB Borecki, A Ziegler, KE North, LA Cupples, F Kronenberg

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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 single nucleotide polymorphisms (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 Eur Conclusions-Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI. (Circ Cardiovasc Genet. 2012;5:100-112.)
Original languageUndefined/Unknown
Pages (from-to)100-112
Number of pages13
JournalCirculation-cardiovascular genetics
Volume5
Issue number1
DOIs
Publication statusPublished - 2012

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