Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities

Ashley Beecham, Chuanhui Dong, Clinton B. Wright, Nicole Dueker, Adam M. Brickman, Liyong Wang, Charles DeCarli, Susan H. Blanton, Tatjana Rundek, Richard Mayeux, Ralph L. Sacco

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genomewide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln (WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1×10-5) and 5 genes from the genebased analysis with p <1×10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p <0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMHassociated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.

Original languageEnglish (US)
Article numbere185
JournalNeurology: Genetics
Volume3
Issue number5
DOIs
StatePublished - Oct 1 2017

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Hispanic Americans
Single Nucleotide Polymorphism
Genome
Brain
African Americans
Genes
White Matter
Population

ASJC Scopus subject areas

  • Clinical Neurology
  • Genetics(clinical)

Cite this

Beecham, A., Dong, C., Wright, C. B., Dueker, N., Brickman, A. M., Wang, L., ... Sacco, R. L. (2017). Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities. Neurology: Genetics, 3(5), [e185]. https://doi.org/10.1212/NXG.0000000000000185

Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities. / Beecham, Ashley; Dong, Chuanhui; Wright, Clinton B.; Dueker, Nicole; Brickman, Adam M.; Wang, Liyong; DeCarli, Charles; Blanton, Susan H.; Rundek, Tatjana; Mayeux, Richard; Sacco, Ralph L.

In: Neurology: Genetics, Vol. 3, No. 5, e185, 01.10.2017.

Research output: Contribution to journalArticle

Beecham, A, Dong, C, Wright, CB, Dueker, N, Brickman, AM, Wang, L, DeCarli, C, Blanton, SH, Rundek, T, Mayeux, R & Sacco, RL 2017, 'Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities', Neurology: Genetics, vol. 3, no. 5, e185. https://doi.org/10.1212/NXG.0000000000000185
Beecham, Ashley ; Dong, Chuanhui ; Wright, Clinton B. ; Dueker, Nicole ; Brickman, Adam M. ; Wang, Liyong ; DeCarli, Charles ; Blanton, Susan H. ; Rundek, Tatjana ; Mayeux, Richard ; Sacco, Ralph L. / Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities. In: Neurology: Genetics. 2017 ; Vol. 3, No. 5.
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abstract = "Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genomewide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln (WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1×10-5) and 5 genes from the genebased analysis with p <1×10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p <0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMHassociated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.",
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AU - Dong, Chuanhui

AU - Wright, Clinton B.

AU - Dueker, Nicole

AU - Brickman, Adam M.

AU - Wang, Liyong

AU - DeCarli, Charles

AU - Blanton, Susan H.

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N2 - Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genomewide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln (WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1×10-5) and 5 genes from the genebased analysis with p <1×10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p <0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMHassociated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.

AB - Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genomewide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln (WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1×10-5) and 5 genes from the genebased analysis with p <1×10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p <0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMHassociated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.

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