Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies
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Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies. / Murabito, Joanne M; White, Charles C; Kavousi, Maryam; Sun, Yan V; Feitosa, Mary F; Nambi, Vijay; Lamina, Claudia; Schillert, Arne; Coassin, Stefan; Bis, Joshua C; Broer, Linda; Crawford, Dana C; Franceschini, Nora; Frikke-Schmidt, Ruth; Haun, Margot; Holewijn, Suzanne; Huffman, Jennifer E; Hwang, Shih-Jen; Kiechl, Stefan; Kollerits, Barbara; Montasser, May E; Nolte, Ilja M; Rudock, Megan E; Senft, Andrea; Teumer, Alexander; van der Harst, Pim; Vitart, Veronique; Waite, Lindsay L; Wood, Andrew R; Wassel, Christina L; Absher, Devin M; Allison, Matthew A; Amin, Najaf; Arnold, Alice; Asselbergs, Folkert W; Aulchenko, Yurii; Bandinelli, Stefania; Barbalic, Maja; Boban, Mladen; Brown-Gentry, Kristin; Couper, David J; Criqui, Michael H; Dehghan, Abbas; den Heijer, Martin; Dieplinger, Benjamin; Ding, Jingzhong; Dörr, Marcus; Espinola-Klein, Christine; Felix, Stephan B; Ferrucci, Luigi; Folsom, Aaron R; Fraedrich, Gustav; Gibson, Quince; Goodloe, Robert; Gunjaca, Grgo; Haltmayer, Meinhard; Heiss, Gerardo; Hofman, Albert; Kieback, Arne; Kiemeney, Lambertus A; Kolcic, Ivana; Kullo, Iftikhar J; Kritchevsky, Stephen B; Lackner, Karl J; Li, Xiaohui; Lieb, Wolfgang; Lohman, Kurt; Meisinger, Christa; Melzer, David; Mohler, Emile R; Mudnic, Ivana; Mueller, Thomas; Navis, Gerjan; Oberhollenzer, Friedrich; Olin, Jeffrey W; O'Connell, Jeff; O'Donnell, Christopher J; Palmas, Walter; Penninx, Brenda W; Petersmann, Astrid; Polasek, Ozren; Psaty, Bruce M; Rantner, Barbara; Rice, Ken; Rivadeneira, Fernando; Rotter, Jerome I; Seldenrijk, Adrie; Stadler, Marietta; Summerer, Monika; Tanaka, Toshiko; Tybjaerg-Hansen, Anne; Uitterlinden, Andre G; van Gilst, Wiek H; Vermeulen, Sita H; Wild, Sarah H; Wild, Philipp S; Willeit, Johann; Zeller, Tanja; Zemunik, Tatijana; Zgaga, Lina; Assimes, Themistocles L; Blankenberg, Stefan; Boerwinkle, Eric; Campbell, Harry; Cooke, John P; de Graaf, Jacqueline; Herrington, David; Kardia, Sharon L R; Mitchell, Braxton D; Murray, Anna; Münzel, Thomas; Newman, Anne B; Oostra, Ben A; Rudan, Igor; Shuldiner, Alan R; Snieder, Harold; van Duijn, Cornelia M; Völker, Uwe; Wright, Alan F; Wichmann, H-Erich; Wilson, James F; Witteman, Jacqueline C M; Liu, Yongmei; Hayward, Caroline; Borecki, Ingrid B; Ziegler, Andreas; North, Kari E; Cupples, L Adrienne; Kronenberg, Florian.
in: CIRC-CARDIOVASC GENE, Jahrgang 5, Nr. 1, 01.02.2012, S. 100-112.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies
AU - Murabito, Joanne M
AU - White, Charles C
AU - Kavousi, Maryam
AU - Sun, Yan V
AU - Feitosa, Mary F
AU - Nambi, Vijay
AU - Lamina, Claudia
AU - Schillert, Arne
AU - Coassin, Stefan
AU - Bis, Joshua C
AU - Broer, Linda
AU - Crawford, Dana C
AU - Franceschini, Nora
AU - Frikke-Schmidt, Ruth
AU - Haun, Margot
AU - Holewijn, Suzanne
AU - Huffman, Jennifer E
AU - Hwang, Shih-Jen
AU - Kiechl, Stefan
AU - Kollerits, Barbara
AU - Montasser, May E
AU - Nolte, Ilja M
AU - Rudock, Megan E
AU - Senft, Andrea
AU - Teumer, Alexander
AU - van der Harst, Pim
AU - Vitart, Veronique
AU - Waite, Lindsay L
AU - Wood, Andrew R
AU - Wassel, Christina L
AU - Absher, Devin M
AU - Allison, Matthew A
AU - Amin, Najaf
AU - Arnold, Alice
AU - Asselbergs, Folkert W
AU - Aulchenko, Yurii
AU - Bandinelli, Stefania
AU - Barbalic, Maja
AU - Boban, Mladen
AU - Brown-Gentry, Kristin
AU - Couper, David J
AU - Criqui, Michael H
AU - Dehghan, Abbas
AU - den Heijer, Martin
AU - Dieplinger, Benjamin
AU - Ding, Jingzhong
AU - Dörr, Marcus
AU - Espinola-Klein, Christine
AU - Felix, Stephan B
AU - Ferrucci, Luigi
AU - Folsom, Aaron R
AU - Fraedrich, Gustav
AU - Gibson, Quince
AU - Goodloe, Robert
AU - Gunjaca, Grgo
AU - Haltmayer, Meinhard
AU - Heiss, Gerardo
AU - Hofman, Albert
AU - Kieback, Arne
AU - Kiemeney, Lambertus A
AU - Kolcic, Ivana
AU - Kullo, Iftikhar J
AU - Kritchevsky, Stephen B
AU - Lackner, Karl J
AU - Li, Xiaohui
AU - Lieb, Wolfgang
AU - Lohman, Kurt
AU - Meisinger, Christa
AU - Melzer, David
AU - Mohler, Emile R
AU - Mudnic, Ivana
AU - Mueller, Thomas
AU - Navis, Gerjan
AU - Oberhollenzer, Friedrich
AU - Olin, Jeffrey W
AU - O'Connell, Jeff
AU - O'Donnell, Christopher J
AU - Palmas, Walter
AU - Penninx, Brenda W
AU - Petersmann, Astrid
AU - Polasek, Ozren
AU - Psaty, Bruce M
AU - Rantner, Barbara
AU - Rice, Ken
AU - Rivadeneira, Fernando
AU - Rotter, Jerome I
AU - Seldenrijk, Adrie
AU - Stadler, Marietta
AU - Summerer, Monika
AU - Tanaka, Toshiko
AU - Tybjaerg-Hansen, Anne
AU - Uitterlinden, Andre G
AU - van Gilst, Wiek H
AU - Vermeulen, Sita H
AU - Wild, Sarah H
AU - Wild, Philipp S
AU - Willeit, Johann
AU - Zeller, Tanja
AU - Zemunik, Tatijana
AU - Zgaga, Lina
AU - Assimes, Themistocles L
AU - Blankenberg, Stefan
AU - Boerwinkle, Eric
AU - Campbell, Harry
AU - Cooke, John P
AU - de Graaf, Jacqueline
AU - Herrington, David
AU - Kardia, Sharon L R
AU - Mitchell, Braxton D
AU - Murray, Anna
AU - Münzel, Thomas
AU - Newman, Anne B
AU - Oostra, Ben A
AU - Rudan, Igor
AU - Shuldiner, Alan R
AU - Snieder, Harold
AU - van Duijn, Cornelia M
AU - Völker, Uwe
AU - Wright, Alan F
AU - Wichmann, H-Erich
AU - Wilson, James F
AU - Witteman, Jacqueline C M
AU - Liu, Yongmei
AU - Hayward, Caroline
AU - Borecki, Ingrid B
AU - Ziegler, Andreas
AU - North, Kari E
AU - Cupples, L Adrienne
AU - Kronenberg, Florian
PY - 2012/2/1
Y1 - 2012/2/1
N2 - 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.
AB - 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.
KW - Adult
KW - Age Factors
KW - Aged
KW - Aged, 80 and over
KW - Alleles
KW - Ankle Brachial Index
KW - Chromosomes, Human, Pair 9
KW - Cohort Studies
KW - Cyclin-Dependent Kinase Inhibitor p15/genetics
KW - Female
KW - Genome-Wide Association Study
KW - Genotype
KW - HapMap Project
KW - Humans
KW - Logistic Models
KW - Male
KW - Middle Aged
KW - Peripheral Vascular Diseases/genetics
KW - Phenotype
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Sex Factors
U2 - 10.1161/CIRCGENETICS.111.961292
DO - 10.1161/CIRCGENETICS.111.961292
M3 - SCORING: Journal article
C2 - 22199011
VL - 5
SP - 100
EP - 112
JO - CIRC-CARDIOVASC GENE
JF - CIRC-CARDIOVASC GENE
SN - 1942-325X
IS - 1
ER -