Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.
- 2018
Available online through MWHC library: 2006 - present
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in =131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in =440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
English
1932-6203
10.1371/journal.pone.0198166 [doi] PMC6005576 [pmc] PONE-D-18-04838 [pii]
*Alcohol Drinking/ep [Epidemiology]
*Alcohol Drinking/ge [Genetics]
*Blood Pressure/ge [Genetics]
*Continental Population Groups
*Hypertension/ep [Epidemiology]
*Hypertension/ge [Genetics]
*Polymorphism, Single Nucleotide
Adolescent
Adult
Aged
Aged, 80 and over
Cohort Studies
Continental Population Groups/ge [Genetics]
Continental Population Groups/sn [Statistics & Numerical Data]
Female
Gene-Environment Interaction
Genetic Predisposition to Disease/ep [Epidemiology]
Genetic Predisposition to Disease/ge [Genetics]
Genome-Wide Association Study
Humans
Male
Middle Aged
Pedigree
Young Adult
MedStar Health Research Institute
Journal Article
Available online through MWHC library: 2006 - present
Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in =131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in =440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
English
1932-6203
10.1371/journal.pone.0198166 [doi] PMC6005576 [pmc] PONE-D-18-04838 [pii]
*Alcohol Drinking/ep [Epidemiology]
*Alcohol Drinking/ge [Genetics]
*Blood Pressure/ge [Genetics]
*Continental Population Groups
*Hypertension/ep [Epidemiology]
*Hypertension/ge [Genetics]
*Polymorphism, Single Nucleotide
Adolescent
Adult
Aged
Aged, 80 and over
Cohort Studies
Continental Population Groups/ge [Genetics]
Continental Population Groups/sn [Statistics & Numerical Data]
Female
Gene-Environment Interaction
Genetic Predisposition to Disease/ep [Epidemiology]
Genetic Predisposition to Disease/ge [Genetics]
Genome-Wide Association Study
Humans
Male
Middle Aged
Pedigree
Young Adult
MedStar Health Research Institute
Journal Article