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Murabito, J.M.* ; White, C.C.* ; Kavousi, M.* ; Sun, Y.V.* ; Feitosa, M.F.* ; Nambi, V.* ; Lamina, C.* ; Schillert, A.* ; Coassin, S.* ; Bis, J.C.* ; Broer, L.* ; Crawford, D.C.* ; Franceschini, N.* ; Frikke-Schmidt, R.* ; Haun, M.* ; Holewijn, S.* ; Huffman, J.E.* ; Hwang, S.J.* ; Kiechl, S.* ; Kollerits, B.* ; Montasser, M.E.* ; Nolte, I.M.* ; Rudock, M.E.* ; Senft, A.* ; Teumer, A.* ; van der Harst, P.* ; Vitart, V.* ; Waite, L.L.* ; Wood, A.R.* ; Wassel, C.L.* ; Absher, D.M.* ; Allison, M.A.* ; Amin, N.* ; Arnold, A.* ; Asselbergs, F.W.* ; Aulchenko, Y.* ; Bandinelli, S.* ; Barbalic, M.* ; Boban, M.* ; Brown-Gentry, K.* ; Couper, D.J.* ; Criqui, M.H.* ; Dehghan, A.* ; den Heijer, M.* ; Dieplinger, B.* ; Ding, J.* ; Dörr, M.* ; Espinola-Klein, C.* ; Felix, S.B.* ; Ferrucci, L.* ; Folsom, A.R.* ; Fraedrich, G.* ; Gibson, Q.* ; Goodloe, R.* ; Gunjaca, G.* ; Haltmayer, M.* ; Heiss, G.* ; Hofman, A.* ; Kieback, A.* ; Kiemeney, L.A.* ; Kolcic, I.* ; Kullo, I.J.* ; Kritchevsky, S.B.* ; Lackner, K.J.* ; Li, X.* ; Lieb, W.* ; Lohman, K.* ; Meisinger, C. ; Melzer, D.* ; Mohler, E.R. 3.r.d.* ; Mudnic, I.* ; Mueller, T.* ; Navis, G.* ; Oberhollenzer, F.* ; Olin, J.W.* ; O'Connell, J.* ; O'Donnell, C.J.* ; Palmas, W.* ; Penninx, B.W.* ; Petersmann, A.* ; Polasek, O.* ; Psaty, B.M.* ; Rantner, B.* ; Rice, K.* ; Rivadeneira, F.* ; Rotter, J.I.* ; Seldenrijk, A.* ; Stadler, M.* ; Summerer, M.* ; Tanaka, T.* ; Tybjaerg-Hansen, A.* ; Uitterlinden, A.G.* ; van Gilst, W.H.* ; Vermeulen, S.H.* ; Wild, S.H.* ; Wild, P.S.* ; Willeit, J.* ; Zeller, T.* ; Zemunik, T.* ; Zgaga, L.* ; Assimes, T.L.* ; Blankenberg, S.* ; Boerwinkle, E.* ; Campbell, H.* ; Cooke, J.P.* ; de Graaf, J.* ; Herrington, D.* ; Kardia, S.L.* ; Mitchell, B.D.* ; Murray, A.* ; Münzel, T.* ; Newman, A.B.* ; Oostra, B.A.* ; Rudan, I.* ; Shuldiner, A.R.* ; Snieder, H.* ; van Duijn, C.M.* ; Völker, U.* ; Wright, A.F.* ; Wichmann, H.-E. ; Wilson, J.F.* ; Witteman, J.C.* ; Liu, Y.* ; Hayward, C.* ; Borecki, I.B.* ; Ziegler, A.* ; North, K.E.* ; Cupples, L.A.* ; Kronenberg, F.*

Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.

Circ. Cardiovasc. Genet. 5, 100-112 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 European ancestry (≈60% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46×10(-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=2.65×10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6×10(-5)), CYBA (rs3794624, P=6.3×10(-5)), and rs1122608 (LDLR, P=0.0026). 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cohort Study ; Genetic Association ; Genome-wide Association Study ; Meta-analysis ; Peripheral Vascular Disease
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Journal Circulation: Cardiovascular Genetics
Quellenangaben Volume: 5, Issue: 1, Pages: 100-112 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Hagerstown, Md
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)