Title :

Genome-wide association analysis of young-onset stroke identifies a locus on chromosome 10q25 near habp2

Author(s) :

Cheng, Yu-Ching [Auteur]
Stanne, Tara M. [Auteur]
Giese, Anne-Katrin [Auteur]
Ho, Weang Kee [Auteur]
Traylor, Matthew [Auteur]
Amouyel, Philippe [Auteur]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Holliday, Elizabeth G. [Auteur]
Malik, Rainer [Auteur]
Xu, Huichun [Auteur]
Kittner, Steven J. [Auteur]
Cole, John W. [Auteur]
O'connell, Jeffrey R. [Auteur]
Danesh, John [Auteur]
Rasheed, Asif [Auteur]
Zhao, Wei [Auteur]
Engelter, Stefan T. [Auteur]
Grond-Ginsbach, Caspar [Auteur]
Kamatani, Yoichiro [Auteur]
Lathrop, Mark [Auteur]
LEYS, Didier [Auteur]
Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV]
Thijs, Vincent N. S. [Auteur]
Metso, Tiina M. [Auteur]
Tatlisumak, Turgut [Auteur]
Pezzini, Alessandro [Auteur]
Parati, Eugenio A. [Auteur]
Norrving, Bo [Auteur]
Bevan, Steve [Auteur]
Rothwell, Peter M. [Auteur]
Sudlow, Cathie L. M. [Auteur]
Slowik, Agnieszka [Auteur]
Lindgren, Arne G. [Auteur]
Walters, Matthew R. [Auteur]
Jannes, Jim [Auteur]
Shen, Jess [Auteur]
Crosslin, David [Auteur]
Doheny, Kimberly [Auteur]
Laurie, Cathy C. [Auteur]
Kanse, Sandip M. [Auteur]
Bis, Joshua C. [Auteur]
Fornage, Myriam [Auteur]
Mosley, Thomas H. [Auteur]
Hopewell, Jemma C. [Auteur]
Strauch, Konstantin [Auteur]
Muller-Nurasyid, Martina [Auteur]
Gieger, Christian [Auteur]
Waldenberger, Melanie [Auteur]
Peters, Annette [Auteur]
Meisinger, Christine [Auteur]
Ikram, Mohammad Arfan [Auteur]
Longstreth, Will T. [Auteur]
Meschia, James F. [Auteur]
Seshadri, Sudha [Auteur]
Sharma, Pankaj [Auteur]
Worrall, Bradford B. [Auteur]
Jern, Christina [Auteur]
Levi, Christopher R. [Auteur]
Dichgans, Martin [Auteur]
Boncoraglio, Giorgio B. [Auteur]
Markus, Hugh S. [Auteur]
Debette, Stéphanie [Auteur]
Rolfs, Arndt [Auteur]
Saleheen, Danish [Auteur]
Mitchell, Braxton D. [Auteur]

Journal title :

Stroke

Abbreviated title :

Stroke

Volume number :

47

Pages :

307-+

Publication date :

2016-02-01

ISSN :

0039-2499

English keyword(s) :

genome-wide analysis
stroke
factor VII
genetics
ischemic stroke

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects ...
Show more >OBJECTIVE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Institut Pasteur de Lille
Université de Lille

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Submission date :

2019-11-27T14:34:46Z