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Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans

BACKGROUND AND PURPOSE—: The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Populati... Full description

Journal Title: Stroke 2015, Vol.46(8), pp.2063-2068
Main Author: Carty, L., Cara
Other Authors: Keene, L., Keith , Cheng, F., Yu-Ching , Meschia, C., James , Chen, J., Wei-Min , Nalls, S., Mike , Bis, B., Joshua , Kittner, K., Steven , Rich, D., Stephen , Tajuddin, H., Salman , Zonderman, M., Alan , Evans, D., Michele , Langefeld, M., Carl , Gottesman, B., Rebecca , Mosley, B., Thomas , Shahar, B., Eyal , Woo, B., Daniel , Yaffe, B., Kristine , Liu, B., Yongmei , Sale, B., Michèle , Dichgans, B., Martin , Malik, B., Rainer , Longstreth, B., W.T. , Mitchell, B., Braxton , Psaty, B., Bruce , Kooperberg, B., Charles , Reiner, B., Alexander , Worrall, B., Bradford , Fornage, B., Myriam
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ID: ISSN: 0039-2499 ; DOI: 10.1161/STROKEAHA.115.009044
Link: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00007670-201508000-00003
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title: Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
format: Article
creator:
  • Carty, L., Cara
  • Keene, L., Keith
  • Cheng, F., Yu-Ching
  • Meschia, C., James
  • Chen, J., Wei-Min
  • Nalls, S., Mike
  • Bis, B., Joshua
  • Kittner, K., Steven
  • Rich, D., Stephen
  • Tajuddin, H., Salman
  • Zonderman, M., Alan
  • Evans, D., Michele
  • Langefeld, M., Carl
  • Gottesman, B., Rebecca
  • Mosley, B., Thomas
  • Shahar, B., Eyal
  • Woo, B., Daniel
  • Yaffe, B., Kristine
  • Liu, B., Yongmei
  • Sale, B., Michèle
  • Dichgans, B., Martin
  • Malik, B., Rainer
  • Longstreth, B., W.T.
  • Mitchell, B., Braxton
  • Psaty, B., Bruce
  • Kooperberg, B., Charles
  • Reiner, B., Alexander
  • Worrall, B., Bradford
  • Fornage, B., Myriam
subjects:
  • Medicine
ispartof: Stroke, 2015, Vol.46(8), pp.2063-2068
description: BACKGROUND AND PURPOSE—: The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. METHODS—: Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P
language:
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identifier: ISSN: 0039-2499 ; DOI: 10.1161/STROKEAHA.115.009044
fulltext: fulltext
issn:
  • 0039-2499
  • 00392499
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titleMeta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
creatorCarty, L., Cara ; Keene, L., Keith ; Cheng, F., Yu-Ching ; Meschia, C., James ; Chen, J., Wei-Min ; Nalls, S., Mike ; Bis, B., Joshua ; Kittner, K., Steven ; Rich, D., Stephen ; Tajuddin, H., Salman ; Zonderman, M., Alan ; Evans, D., Michele ; Langefeld, M., Carl ; Gottesman, B., Rebecca ; Mosley, B., Thomas ; Shahar, B., Eyal ; Woo, B., Daniel ; Yaffe, B., Kristine ; Liu, B., Yongmei ; Sale, B., Michèle ; Dichgans, B., Martin ; Malik, B., Rainer ; Longstreth, B., W.T. ; Mitchell, B., Braxton ; Psaty, B., Bruce ; Kooperberg, B., Charles ; Reiner, B., Alexander ; Worrall, B., Bradford ; Fornage, B., Myriam
ispartofStroke, 2015, Vol.46(8), pp.2063-2068
identifierISSN: 0039-2499 ; DOI: 10.1161/STROKEAHA.115.009044
descriptionBACKGROUND AND PURPOSE—: The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. METHODS—: Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P<10 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. RESULTS—: The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10) in African Americans. Nominal associations (P<10) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood–brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. CONCLUSIONS—: We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.
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1Keene, L, Keith
2Cheng, F, Yu-Ching
3Meschia, C, James
4Chen, J, Wei-Min
5Nalls, S, Mike
6Bis, B, Joshua
7Kittner, K, Steven
8Rich, D, Stephen
9Tajuddin, H, Salman
10Zonderman, M, Alan
11Evans, D, Michele
12Langefeld, M, Carl
13Gottesman, B, Rebecca
14Mosley, B, Thomas
15Shahar, B, Eyal
16Woo, B, Daniel
17Yaffe, B, Kristine
18Liu, B, Yongmei
19Sale, B, Michèle
20Dichgans, B, Martin
21Malik, B, Rainer
22Longstreth, B, W.T
23Mitchell, B, Braxton
24Psaty, B, Bruce
25Kooperberg, B, Charles
26Reiner, B, Alexander
27Worrall, B, Bradford
28Fornage, B, Myriam
titleMeta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
descriptionBACKGROUND AND PURPOSE—: The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. METHODS—: Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P<10 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. RESULTS—: The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10) in African Americans. Nominal associations (P<10) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood–brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. CONCLUSIONS—: We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.
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010.1161/STROKEAHA.115.009044
1© 2015 American Heart Association, Inc.
2Lippincott Williams & Wilkins - Journals
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titleMeta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
authorCarty, L., Cara ; Keene, L., Keith ; Cheng, F., Yu-Ching ; Meschia, C., James ; Chen, J., Wei-Min ; Nalls, S., Mike ; Bis, B., Joshua ; Kittner, K., Steven ; Rich, D., Stephen ; Tajuddin, H., Salman ; Zonderman, M., Alan ; Evans, D., Michele ; Langefeld, M., Carl ; Gottesman, B., Rebecca ; Mosley, B., Thomas ; Shahar, B., Eyal ; Woo, B., Daniel ; Yaffe, B., Kristine ; Liu, B., Yongmei ; Sale, B., Michèle ; Dichgans, B., Martin ; Malik, B., Rainer ; Longstreth, B., W.T. ; Mitchell, B., Braxton ; Psaty, B., Bruce ; Kooperberg, B., Charles ; Reiner, B., Alexander ; Worrall, B., Bradford ; Fornage, B., Myriam
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9Tajuddin, H., Salman
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16Woo, B., Daniel
17Yaffe, B., Kristine
18Liu, B., Yongmei
19Sale, B., Michèle
20Dichgans, B., Martin
21Malik, B., Rainer
22Longstreth, B., W.T.
23Mitchell, B., Braxton
24Psaty, B., Bruce
25Kooperberg, B., Charles
26Reiner, B., Alexander
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28Fornage, B., Myriam
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atitleMeta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans
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abstractBACKGROUND AND PURPOSE—: The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. METHODS—: Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P<10 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. RESULTS—: The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P=3.9×10) in African Americans. Nominal associations (P<10) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing (PTPRG, CDC5L), platelet function (HPS4), blood–brain barrier permeability (CLDN17), immune response (ELTD1, WDFY4, and IL1F10-IL1RN), and histone modification (HDAC9). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 (P=0.03), and 1p31.1 (P=0.018). Four of 7 previously reported ischemic stroke loci (PITX2, HDAC9, CDKN2A/CDKN2B, and ZFHX3) were nominally associated (P<0.05) with stroke in COMPASS. CONCLUSIONS—: We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.
pub© 2015 American Heart Association, Inc.
doi10.1161/STROKEAHA.115.009044
eissn15244628
date2015-08