Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Gasparini Paolo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 × 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 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 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.

Original languageEnglish
Article numbere0198166
JournalPLoS One
Volume13
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Blood pressure
blood pressure
ancestry
alcohols
Genes
Alcohols
Alcohol Drinking
Blood Pressure
loci
genes
Pressure regulation
Meta-Analysis
hypertension
Hypertension
Genome-Wide Association Study
Genetic Testing
meta-analysis
alcohol drinking
risk factors
Nucleotides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. / Gasparini Paolo.

In: PLoS One, Vol. 13, No. 6, e0198166, 01.06.2018.

Research output: Contribution to journalArticle

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title = "Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries",
abstract = "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 × 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 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 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.",
author = "{Gasparini Paolo} and Feitosa, {Mary F.} and Kraja, {Aldi T.} and Chasman, {Daniel I.} and Sung, {Yun J.} and Winkler, {Thomas W.} and Ioanna Ntalla and Xiuqing Guo and Nora Franceschini and Cheng, {Ching Yu} and Xueling Sim and Dina Vojinovic and Jonathan Marten and Musani, {Solomon K.} and Changwei Li and Bentley, {Amy R.} and Brown, {Michael R.} and Karen Schwander and Richard, {Melissa A.} and Raymond Noordam and Hugues Aschard and Bartz, {Traci M.} and Bielak, {Lawrence F.} and Rajkumar Dorajoo and Virginia Fisher and Hartwig, {Fernando P.} and Horimoto, {Andrea R.V.R.} and Lohman, {Kurt K.} and Manning, {Alisa K.} and Tuomo Rankinen and Smith, {Albert V.} and Tajuddin, {Salman M.} and Wojczynski, {Mary K.} and Maris Alver and Mathilde Boissel and Qiuyin Cai and Archie Campbell and Chai, {Jin Fang} and Xu Chen and Jasmin Divers and Chuan Gao and Anuj Goel and Yanick Hagemeijer and Harris, {Sarah E.} and Meian He and Hsu, {Fang Chi} and Jackson, {Anne U.} and Mika K{\"a}h{\"o}nen and Anuradhani Kasturiratne and Antonietta Robino and Paolo Gasparini",
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AU - Noordam, Raymond

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AU - Dorajoo, Rajkumar

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AU - Hartwig, Fernando P.

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AU - Jackson, Anne U.

AU - Kähönen, Mika

AU - Kasturiratne, Anuradhani

AU - Robino, Antonietta

AU - Gasparini, Paolo

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