Meta-analysis of Genome-wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage | Zendy

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Meta-analysis of Genome-wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage

Author(s) -

Daniel Woo,

Guido J. Falcone,

William J. Devan,

W. Mark Brown,

Alessandro Biffi,

Timothy D. Howard,

Christopher D. Anderson,

H. Bart Brouwers,

Valerie Valant,

Thomas W.K. Battey,

Farid Radmanesh,

Miriam R. Raffeld,

Sylvia Baedorf-Kassis,

Ranjan Deka,

Jessica G. Woo,

Lisa J. Martin,

Mary Haverbusch,

Charles J. Moomaw,

Guangyun Sun,

Joseph P. Broderick,

Matthew L. Flaherty,

Sharyl Martini,

Dawn Kleindorfer,

Brett Kissela,

Mary E. Comeau,

Jeremiasz Jagiełła,

Helena Schmidt,

Paul Freudenberger,

Alexander Pichler,

Christian Enzinger,

Björn M. Hansen,

Bo Norrving,

Jordi JiménezConde,

Eva GiraltSteinhauer,

Roberto Elosúa,

Elisa CuadradoGodia,

Carolina SorianoTárraga,

Jaume Roquer,

Peter Kraft,

Alison Ayres,

Kristin Schwab,

Jacob L. McCauley,

Joanna Pera,

Andrzej Urbanik,

Natalia S. Rost,

Joshua N. Goldstein,

Anand Viswanathan,

Eva-Maria Stögerer,

David Tirschwell,

Magdy Selim,

Devin L. Brown,

Scott Silliman,

Bradford B. Worrall,

James F. Meschia,

Chelsea S. Kidwell,

Joan Montaner,

Israel FernándezCadenas,

Pilar Delgado,

Rainer Malik,

Martin Dichgans,

Steven M. Greenberg,

Peter M. Rothwell,

Arne Lindgren,

Agnieszka Słowik,

Reinhold Schmidt,

Carl D. Langefeld,

Jonathan Rosand

Publication year - 2014

Publication title -

the american journal of human genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.661

H-Index - 302

eISSN - 1537-6605

pISSN - 0002-9297

DOI - 10.1016/j.ajhg.2014.02.012

Subject(s) - intracerebral hemorrhage , medicine , cohort , genome wide association study , genotyping , odds ratio , case control study , heritability , cohort study , genotype , genetics , single nucleotide polymorphism , biology , gene , subarachnoid hemorrhage

Intracerebral hemorrhage (ICH) is the stroke subtype with the worst prognosis and has no established acute treatment. ICH is classified as lobar or nonlobar based on the location of ruptured blood vessels within the brain. These different locations also signal different underlying vascular pathologies. Heritability estimates indicate a substantial genetic contribution to risk of ICH in both locations. We report a genome-wide association study of this condition that meta-analyzed data from six studies that enrolled individuals of European ancestry. Case subjects were ascertained by neurologists blinded to genotype data and classified as lobar or nonlobar based on brain computed tomography. ICH-free control subjects were sampled from ambulatory clinics or random digit dialing. Replication of signals identified in the discovery cohort with p < 1 × 10(-6) was pursued in an independent multiethnic sample utilizing both direct and genome-wide genotyping. The discovery phase included a case cohort of 1,545 individuals (664 lobar and 881 nonlobar cases) and a control cohort of 1,481 individuals and identified two susceptibility loci: for lobar ICH, chromosomal region 12q21.1 (rs11179580, odds ratio [OR] = 1.56, p = 7.0 × 10(-8)); and for nonlobar ICH, chromosomal region 1q22 (rs2984613, OR = 1.44, p = 1.6 × 10(-8)). The replication included a case cohort of 1,681 individuals (484 lobar and 1,194 nonlobar cases) and a control cohort of 2,261 individuals and corroborated the association for 1q22 (p = 6.5 × 10(-4); meta-analysis p = 2.2 × 10(-10)) but not for 12q21.1 (p = 0.55; meta-analysis p = 2.6 × 10(-5)). These results demonstrate biological heterogeneity across ICH subtypes and highlight the importance of ascertaining ICH cases accordingly.

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