Rare Coding Variation and Risk of Intracerebral Hemorrhage

Farid Radmanesh; Guido J. Falcone; Christopher D. Anderson; David McWilliams; William J. Devan; W. Mark Brown; Thomas W.K. Battey; Alison M. Ayres; Miriam R. Raffeld; Kristin Schwab; Guangyun Sun; Ranjan Deka; Anand Viswanathan; Joshua N. Goldstein; Steven M. Greenberg; David L. Tirschwell; Scott L. Silliman; Magdy Selim; James F. Meschia; Devin L. Brown; Bradford B. Worrall; Carl D. Langefeld; Daniel Woo; Jonathan Rosand

doi:10.1161/STROKEAHA.115.009838

Rare Coding Variation and Risk of Intracerebral Hemorrhage

Farid Radmanesh
, Guido J. Falcone
, Christopher D. Anderson
, David McWilliams
, William J. Devan
, W. Mark Brown
, Thomas W.K. Battey
, Alison M. Ayres
, Miriam R. Raffeld
, Kristin Schwab
, Guangyun Sun
, Ranjan Deka
, Anand Viswanathan
, Joshua N. Goldstein
, Steven M. Greenberg
, David L. Tirschwell
, Scott L. Silliman
, Magdy Selim
, James F. Meschia
, Devin L. Brown

Bradford B. Worrall, Carl D. Langefeld, Daniel Woo, Jonathan Rosand

Neurology

The Broad Institute of MIT and Harvard

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English
Pages (from-to)	2299-2301
Number of pages	3
Journal	Stroke
Volume	46
Issue number	8
DOIs	https://doi.org/10.1161/STROKEAHA.115.009838
State	Published - Aug 1 2015

Keywords

apolipoproteins E
cerebral hemorrhage
genome-wide association study

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Radmanesh, F., Falcone, G. J., Anderson, C. D., McWilliams, D., Devan, W. J., Brown, W. M., Battey, T. W. K., Ayres, A. M., Raffeld, M. R., Schwab, K., Sun, G., Deka, R., Viswanathan, A., Goldstein, J. N., Greenberg, S. M., Tirschwell, D. L., Silliman, S. L., Selim, M., Meschia, J. F., ... Rosand, J. (2015). Rare Coding Variation and Risk of Intracerebral Hemorrhage. Stroke, 46(8), 2299-2301. https://doi.org/10.1161/STROKEAHA.115.009838

@article{a11dff3dddf44c3fb42cc4143d7f8e5c,

title = "Rare Coding Variation and Risk of Intracerebral Hemorrhage",

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.",

keywords = "apolipoproteins E, cerebral hemorrhage, genome-wide association study",

author = "Farid Radmanesh and Falcone, \{Guido J.\} and Anderson, \{Christopher D.\} and David McWilliams and Devan, \{William J.\} and Brown, \{W. Mark\} and Battey, \{Thomas W.K.\} and Ayres, \{Alison M.\} and Raffeld, \{Miriam R.\} and Kristin Schwab and Guangyun Sun and Ranjan Deka and Anand Viswanathan and Goldstein, \{Joshua N.\} and Greenberg, \{Steven M.\} and Tirschwell, \{David L.\} and Silliman, \{Scott L.\} and Magdy Selim and Meschia, \{James F.\} and Brown, \{Devin L.\} and Worrall, \{Bradford B.\} and Langefeld, \{Carl D.\} and Daniel Woo and Jonathan Rosand",

note = "Publisher Copyright: {\textcopyright} 2015 American Heart Association, Inc.",

year = "2015",

month = aug,

day = "1",

doi = "10.1161/STROKEAHA.115.009838",

language = "English",

volume = "46",

pages = "2299--2301",

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Radmanesh, F, Falcone, GJ, Anderson, CD, McWilliams, D, Devan, WJ, Brown, WM, Battey, TWK, Ayres, AM, Raffeld, MR, Schwab, K, Sun, G, Deka, R, Viswanathan, A, Goldstein, JN, Greenberg, SM, Tirschwell, DL, Silliman, SL, Selim, M, Meschia, JF, Brown, DL, Worrall, BB, Langefeld, CD, Woo, D & Rosand, J 2015, 'Rare Coding Variation and Risk of Intracerebral Hemorrhage', Stroke, vol. 46, no. 8, pp. 2299-2301. https://doi.org/10.1161/STROKEAHA.115.009838

TY - JOUR

T1 - Rare Coding Variation and Risk of Intracerebral Hemorrhage

AU - Radmanesh, Farid

AU - Falcone, Guido J.

AU - Anderson, Christopher D.

AU - McWilliams, David

AU - Devan, William J.

AU - Brown, W. Mark

AU - Battey, Thomas W.K.

AU - Ayres, Alison M.

AU - Raffeld, Miriam R.

AU - Schwab, Kristin

AU - Sun, Guangyun

AU - Deka, Ranjan

AU - Viswanathan, Anand

AU - Goldstein, Joshua N.

AU - Greenberg, Steven M.

AU - Tirschwell, David L.

AU - Silliman, Scott L.

AU - Selim, Magdy

AU - Meschia, James F.

AU - Brown, Devin L.

AU - Worrall, Bradford B.

AU - Langefeld, Carl D.

AU - Woo, Daniel

AU - Rosand, Jonathan

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

KW - apolipoproteins E

KW - cerebral hemorrhage

KW - genome-wide association study

UR - https://www.scopus.com/pages/publications/84964697534

U2 - 10.1161/STROKEAHA.115.009838

DO - 10.1161/STROKEAHA.115.009838

M3 - Article

C2 - 26111891

AN - SCOPUS:84964697534

SN - 0039-2499

VL - 46

SP - 2299

EP - 2301

JO - Stroke

JF - Stroke

IS - 8

ER -

Rare Coding Variation and Risk of Intracerebral Hemorrhage

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Keywords

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