Farid Radmanesh1, Guido J Falcone1, Christopher D Anderson1, David McWilliams1, William J Devan1, W Mark Brown1, Thomas W K Battey1, Alison M Ayres1, Miriam R Raffeld1, Kristin Schwab1, Guangyun Sun1, Ranjan Deka1, Anand Viswanathan1, Joshua N Goldstein1, Steven M Greenberg1, David L Tirschwell1, Scott L Silliman1, Magdy Selim1, James F Meschia1, Devin L Brown1, Bradford B Worrall1, Carl D Langefeld1, Daniel Woo1, Jonathan Rosand2. 1. From the Center for Human Genetic Research (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), J. Philip Kistler Stroke Research Center (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., A.M.A., M.R.R., K.S., A.V., S.M.G., J.R.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.); Department of Biostatistical Sciences, Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC (D.M., W.M.B., C.D.L.); Quinnipiac University, Frank H. Netter MD School of Medicine, Hamden, CT (W.J.D.); Department of Environmental Health (G.S., R.D.) and Department of Neurology and Rehabilitation (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology, Harborview Medical Center, University of Washington, Seattle (D.L.T.); Department of Neurology, University of Florida College of Medicine, Jacksonville (S.L.S.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (M.S.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.F.M.); Department of Neurology, University of Michigan Health System, Ann Arbor (D.L.B.); and Departments of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville (B.B.W.). 2. From the Center for Human Genetic Research (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), Division of Neurocritical Care and Emergency Neurology, Department of Neurology (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.), J. Philip Kistler Stroke Research Center (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., A.M.A., M.R.R., K.S., A.V., S.M.G., J.R.), and Department of Emergency Medicine (J.N.G.), Massachusetts General Hospital, Boston; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (F.R., G.J.F., C.D.A., W.J.D., T.W.K.B., M.R.R., J.R.); Department of Biostatistical Sciences, Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC (D.M., W.M.B., C.D.L.); Quinnipiac University, Frank H. Netter MD School of Medicine, Hamden, CT (W.J.D.); Department of Environmental Health (G.S., R.D.) and Department of Neurology and Rehabilitation (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology, Harborview Medical Center, University of Washington, Seattle (D.L.T.); Department of Neurology, University of Florida College of Medicine, Jacksonville (S.L.S.); Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA (M.S.); Department of Neurology, Mayo Clinic, Jacksonville, FL (J.F.M.); Department of Neurology, University of Michigan Health System, Ann Arbor (D.L.B.); and Departments of Neurology and Public Health Sciences, University of Virginia Health System, Charlottesville (B.B.W.). jrosand@partners.org.
Abstract
BACKGROUND AND PURPOSE: Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. METHODS: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. RESULTS: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. CONCLUSIONS: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.
BACKGROUND AND PURPOSE:Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. METHODS: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. RESULTS: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. CONCLUSIONS: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.
Authors: 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 R Martini; Dawn O Kleindorfer; Brett Kissela; Mary E Comeau; Jeremiasz M Jagiella; Helena Schmidt; Paul Freudenberger; Alexander Pichler; Christian Enzinger; Björn M Hansen; Bo Norrving; Jordi Jimenez-Conde; Eva Giralt-Steinhauer; Roberto Elosua; Elisa Cuadrado-Godia; Carolina Soriano; Jaume Roquer; Peter Kraft; Alison M Ayres; Kristin Schwab; Jacob L McCauley; Joanna Pera; Andrzej Urbanik; Natalia S Rost; Joshua N Goldstein; Anand Viswanathan; Eva-Maria Stögerer; David L Tirschwell; Magdy Selim; Devin L Brown; Scott L Silliman; Bradford B Worrall; James F Meschia; Chelsea S Kidwell; Joan Montaner; Israel Fernandez-Cadenas; Pilar Delgado; Rainer Malik; Martin Dichgans; Steven M Greenberg; Peter M Rothwell; Arne Lindgren; Agnieszka Slowik; Reinhold Schmidt; Carl D Langefeld; Jonathan Rosand Journal: Am J Hum Genet Date: 2014-03-20 Impact factor: 11.025
Authors: Seunggeun Lee; Mary J Emond; Michael J Bamshad; Kathleen C Barnes; Mark J Rieder; Deborah A Nickerson; David C Christiani; Mark M Wurfel; Xihong Lin Journal: Am J Hum Genet Date: 2012-08-02 Impact factor: 11.025
Authors: Marion Jeanne; Cassandre Labelle-Dumais; Jeff Jorgensen; W Berkeley Kauffman; Grazia M Mancini; Jack Favor; Valerie Valant; Steven M Greenberg; Jonathan Rosand; Douglas B Gould Journal: Am J Hum Genet Date: 2011-12-29 Impact factor: 11.025
Authors: Louise A Donnelly; Colin N A Palmer; Adrian L Whitley; Chim Choy Lang; Alex S F Doney; Andrew D Morris; Peter T Donnan Journal: Pharmacogenet Genomics Date: 2008-04 Impact factor: 2.089
Authors: William J Devan; Guido J Falcone; Christopher D Anderson; Jeremiasz M Jagiella; Helena Schmidt; Björn M Hansen; Jordi Jimenez-Conde; Eva Giralt-Steinhauer; Elisa Cuadrado-Godia; Carolina Soriano; Alison M Ayres; Kristin Schwab; Sylvia Baedorf Kassis; Valerie Valant; Joanna Pera; Andrzej Urbanik; Anand Viswanathan; Natalia S Rost; Joshua N Goldstein; Paul Freudenberger; Eva-Maria Stögerer; Bo Norrving; David L Tirschwell; Magdy Selim; Devin L Brown; Scott L Silliman; Bradford B Worrall; James F Meschia; Chelsea S Kidwell; Joan Montaner; Israel Fernandez-Cadenas; Pilar Delgado; Steven M Greenberg; Jaume Roquer; Arne Lindgren; Agnieszka Slowik; Reinhold Schmidt; Daniel Woo; Jonathan Rosand; Alessandro Biffi Journal: Stroke Date: 2013-04-04 Impact factor: 7.914
Authors: Alessandro Biffi; Akshata Sonni; Christopher D Anderson; Brett Kissela; Jeremiasz M Jagiella; Helena Schmidt; Jordi Jimenez-Conde; Björn M Hansen; Israel Fernandez-Cadenas; Lynelle Cortellini; Alison Ayres; Kristin Schwab; Karol Juchniewicz; Andrzej Urbanik; Natalia S Rost; Anand Viswanathan; Thomas Seifert-Held; Eva-Maria Stoegerer; Marta Tomás; Raquel Rabionet; Xavier Estivill; Devin L Brown; Scott L Silliman; Magdy Selim; Bradford B Worrall; James F Meschia; Joan Montaner; Arne Lindgren; Jaume Roquer; Reinhold Schmidt; Steven M Greenberg; Agnieszka Slowik; Joseph P Broderick; Daniel Woo; Jonathan Rosand Journal: Ann Neurol Date: 2010-12 Impact factor: 10.422
Authors: Femke N G van 't Hof; Dongbing Lai; Jessica van Setten; Michiel L Bots; Ilonca Vaartjes; Joseph Broderick; Daniel Woo; Tatiana Foroud; Gabriel J E Rinkel; Paul I W de Bakker; Ynte M Ruigrok Journal: Neurology Date: 2019-11-15 Impact factor: 9.910