TY - JOUR
T1 - Meta-analysis of genome-wide association studies identifies 1q22 as a susceptibility locus for intracerebral hemorrhage
AU - Woo, Daniel
AU - Falcone, Guido J.
AU - Devan, William J.
AU - Brown, W. Mark
AU - Biffi, Alessandro
AU - Howard, Timothy D.
AU - Anderson, Christopher D.
AU - Brouwers, H. Bart
AU - Valant, Valerie
AU - Battey, Thomas W.K.
AU - Radmanesh, Farid
AU - Raffeld, Miriam R.
AU - Baedorf-Kassis, Sylvia
AU - Deka, Ranjan
AU - Woo, Jessica G.
AU - Martin, Lisa J.
AU - Haverbusch, Mary
AU - Moomaw, Charles J.
AU - Sun, Guangyun
AU - Broderick, Joseph P.
AU - Flaherty, Matthew L.
AU - Martini, Sharyl R.
AU - Kleindorfer, Dawn O.
AU - Kissela, Brett
AU - Comeau, Mary E.
AU - Jagiella, Jeremiasz M.
AU - Schmidt, Helena
AU - Freudenberger, Paul
AU - Pichler, Alexander
AU - Enzinger, Christian
AU - Hansen, Björn M.
AU - Norrving, Bo
AU - Jimenez-Conde, Jordi
AU - Giralt-Steinhauer, Eva
AU - Elosua, Roberto
AU - Cuadrado-Godia, Elisa
AU - Soriano, Carolina
AU - Roquer, Jaume
AU - Kraft, Peter
AU - Ayres, Alison M.
AU - Schwab, Kristin
AU - McCauley, Jacob L.
AU - Pera, Joanna
AU - Urbanik, Andrzej
AU - Rost, Natalia S.
AU - Goldstein, Joshua N.
AU - Viswanathan, Anand
AU - Stögerer, Eva Maria
AU - Tirschwell, David L.
AU - Selim, Magdy
AU - Brown, Devin L.
AU - Silliman, Scott L.
AU - Worrall, Bradford B.
AU - Meschia, James F.
AU - Kidwell, Chelsea S.
AU - Montaner, Joan
AU - Fernandez-Cadenas, Israel
AU - Delgado, Pilar
AU - Malik, Rainer
AU - Dichgans, Martin
AU - Greenberg, Steven M.
AU - Rothwell, Peter M.
AU - Lindgren, Arne
AU - Slowik, Agnieszka
AU - Schmidt, Reinhold
AU - Langefeld, Carl D.
AU - Rosand, Jonathan
N1 - Funding Information:
We thank the Biorepository and Center for Genome Technology (University of Miami) (specifically Sandra West, Ioanna Konidari, and Susan Slifer) and Miguel Hernán for providing expert advice. Computing support, in part, provided by the Wake Forest Center for Public Health Genomics. Funding entities had no direct involvement in study design; data collection, analysis, and interpretation; writing of the manuscript; or the decision to submit for publication. Funding provided as follows: GERFHS, NIH grants NS36695 and NS30678; GOCHA, NIH grant R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, and the University of Michigan General Clinical Research Center M01 RR000042; ERICH, NIH grant NS069763; HM-ICH, Instituto de Salud Carlos III with the grants “Registro BASICMAR” Funding for Research in Health (PI051737), “GWALA project” from Fondos de Investigación Sanitaria ISC III (PI10/02064), and Fondos FEDER/EDRF Red de Investigación Cardiovascular (RD12/0042); JUHSS, Polish Ministry of Education grant N402 083934; LSR, Lund University, Region Skåne, the Swedish Research Council (K2010-61X-20378-04-3), the Swedish Stroke Association, the Freemasons Lodge of Instruction EOS in Lund, and the King Gustaf V and Queen Victoria’s foundations; G.J.F. and H.B.B., NIH SPOTRIAS fellowship P50NS061343; C.D.D., fellowship from the American Brain Foundation; J.N.G., NIH grant 5K23NS059774; P.M.R., awards from the NIHR and the Wellcome Trust; M.S., NIH grant U01 NS074425; and D.L.B., NIH grants R01 NS062675, R01 HL098065, R01 NS070941, and R18 HS017690, the Blue Cross Blue Shield of Michigan Foundation, Michigan Department of Community Health, and the University of Michigan.
PY - 2014/4/3
Y1 - 2014/4/3
N2 - 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.
AB - 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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U2 - 10.1016/j.ajhg.2014.02.012
DO - 10.1016/j.ajhg.2014.02.012
M3 - Article
C2 - 24656865
AN - SCOPUS:84898001150
SN - 0002-9297
VL - 94
SP - 511
EP - 521
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -