TY - JOUR
T1 - Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
AU - Bellenguez, Céline
AU - Bevan, Steve
AU - Gschwendtner, Andreas
AU - Spencer, Chris C A
AU - Burgess, Annette I
AU - Pirinen, Matti
AU - Jackson, Caroline A
AU - Traylor, Matthew
AU - Strange, Amy
AU - Su, Zhan
AU - Band, Gavin
AU - Syme, Paul D
AU - Malik, Rainer
AU - Pera, Joanna
AU - Norrving, Bo
AU - Lemmens, Robin
AU - Freeman, Colin
AU - Schanz, Renata
AU - James, Tom
AU - Poole, Deborah
AU - Murphy, Lee
AU - Segal, Helen
AU - Cortellini, Lynelle
AU - Cheng, Yu-Ching
AU - Woo, Daniel
AU - Nalls, Michael A
AU - Müller-Myhsok, Bertram
AU - Meisinger, Christa
AU - Seedorf, Udo
AU - Ross-Adams, Helen
AU - Boonen, Steven
AU - Wloch-Kopec, Dorota
AU - Valant, Valerie
AU - Slark, Julia
AU - Furie, Karen
AU - Delavaran, Hossein
AU - Langford, Cordelia
AU - Deloukas, Panos
AU - Edkins, Sarah
AU - Hunt, Sarah
AU - Gray, Emma
AU - Dronov, Serge
AU - Peltonen, Leena
AU - Gretarsdottir, Solveig
AU - Thorleifsson, Gudmar
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
AU - Boncoraglio, Giorgio B
AU - Parati, Eugenio A
AU - Macleod, Mary Joan
AU - The International Stroke Genetics Consortium (ISGC)
AU - The Wellcome Trust Case Control Consortium 2 (WTCCC2)
PY - 2012/3
Y1 - 2012/3
N2 - Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
AB - Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
KW - stroke
KW - genetics
U2 - 10.1038/ng.1081
DO - 10.1038/ng.1081
M3 - Letter
C2 - 22306652
SN - 1061-4036
VL - 44
SP - 328
EP - 333
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -