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Meta-Analysis of Genome-Wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage.

Woo, Daniel; Falcone, Guido J; Devan, William J; Brown, W Mark; Biffi, Alessandro; Howard, Timothy D; Anderson, Christopher D; Brouwers, H Bart; Valant, Valerie and Battey, Thomas W K, et al. (2014) In American Journal of Human Genetics
Abstract
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... (More)
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. (Less)
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American Journal of Human Genetics
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Cell Press
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  • pmid:24656865
  • wos:000333765300003
  • scopus:84898001150
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0002-9297
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10.1016/j.ajhg.2014.02.012
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English
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884ab5d6-649a-45d8-a9a2-3dbb332eacce (old id 4379914)
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2014-04-03 21:00:18
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@article{884ab5d6-649a-45d8-a9a2-3dbb332eacce,
  abstract     = {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 &lt; 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.},
  author       = {Woo, Daniel and Falcone, Guido J and Devan, William J and Brown, W Mark and Biffi, Alessandro and Howard, Timothy D and Anderson, Christopher D and Brouwers, H Bart and Valant, Valerie and Battey, Thomas W K and Radmanesh, Farid and Raffeld, Miriam R and Baedorf-Kassis, Sylvia and Deka, Ranjan and Woo, Jessica G and Martin, Lisa J and Haverbusch, Mary and Moomaw, Charles J and Sun, Guangyun and Broderick, Joseph P and Flaherty, Matthew L and Martini, Sharyl R and Kleindorfer, Dawn O and Kissela, Brett and Comeau, Mary E and Jagiella, Jeremiasz M and Schmidt, Helena and Freudenberger, Paul and Pichler, Alexander and Enzinger, Christian and Hansen, Björn and Norrving, Bo and Jimenez-Conde, Jordi and Giralt-Steinhauer, Eva and Elosua, Roberto and Cuadrado-Godia, Elisa and Soriano, Carolina and Roquer, Jaume and Kraft, Peter and Ayres, Alison M and Schwab, Kristin and McCauley, Jacob L and Pera, Joanna and Urbanik, Andrzej and Rost, Natalia S and Goldstein, Joshua N and Viswanathan, Anand and Stögerer, Eva-Maria and Tirschwell, David L and Selim, Magdy and Brown, Devin L and Silliman, Scott L and Worrall, Bradford B and Meschia, James F and Kidwell, Chelsea S and Montaner, Joan and Fernandez-Cadenas, Israel and Delgado, Pilar and Malik, Rainer and Dichgans, Martin and Greenberg, Steven M and Rothwell, Peter M and Lindgren, Arne and Slowik, Agnieszka and Schmidt, Reinhold and Langefeld, Carl D and Rosand, Jonathan},
  issn         = {0002-9297},
  language     = {eng},
  month        = {03},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Meta-Analysis of Genome-Wide Association Studies Identifies 1q22 as a Susceptibility Locus for Intracerebral Hemorrhage.},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2014.02.012},
  year         = {2014},
}