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

Feitosa, M. F. and Kraja, A. T. and Chasman, D. I. and Sung, Y. J. and Winkler, T. W. and Ntalla, I. and Guo, X. and Franceschini, N. and Cheng, C. Y. and Sim, X. and Vojinovic, D. and Marten, J. and Musani, S. K. and Li, C. and Bentley, A. R. and Brown, M. R. and Schwander, K. and Richard, M. A. and Noordam, R. and Aschard, H. and Bartz, T. M. and Bielak, L. F. and Dorajoo, R. and Fisher, V. and Hartwig, F. P. and Horimoto, A. R. V. R. and Lohman, K. K. and Manning, A. K. and Rankinen, T. and Smith, A. V. and Tajuddin, S. M. and Wojczynski, M. K. and Alver, M. and Boissel, M. and Cai, Q. and Campbell, A. and Chai, J. F. and Chen, X. and Divers, J. and Gao, C. and Goel, A. and Hagemeijer, Y. and Harris, S. E. and He, M. and Hsu, F. C. and Jackson, A. U. and Kähönen, M. and Kasturiratne, A. and Komulainen, P. and Kühnel, B. and Laguzzi, F. and Luan, J. and Matoba, N. and Nolte, I. M. and Padmanabhan, S. and Riaz, M. and Rueedi, R. and Robino, A. and Said, M. A. and Scott, R. A. and Sofer, T. and Stančáková, A. and Takeuchi, F. and Tayo, B. O. and Van Der Most, P. J. and Varga, T. V. and Vitart, V. and Wang, Y. and Ware, E. B. and Warren, H. R. and Weiss, S. and Wen, W. and Yanek, L. R. and Zhang, W. and Zhao, J. H. and Afaq, S. and Amin, N. and Amini, M. and Arking, D. E. and Aung, T. and Boerwinkle, E. and Borecki, I. and Broeckel, U. and Brown, M. and Brumat, M. and Burke, G. L. and Canouil, M. and Chakravarti, A. and Charumathi, S. and Chen, Y. D. I. and Connell, J. M. and Correa, A. and De Las Fuentes, L. and De Mutsert, R. and De Silva, H. J. and Deng, X. and Ding, J. and Duan, Q. and Eaton, C. B. and Ehret, G. (2018) Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. PLoS ONE, 13 (6).

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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. © 2018 Public Library of Science. All Rights Reserved.

Item Type: Article
Additional Information: Cited By :4 Export Date: 16 February 2020 CODEN: POLNC
Uncontrolled Keywords: alcohol ACE gene ADRB1 gene adult African AGT gene alcohol consumption ancestry group Article Asian BLK gene blood pressure blood pressure regulation Brazilian cardiomegaly cardiovascular disease CATSPER2 gene chromosome 16q chromosome 8p cohort analysis controlled study correlation analysis diastolic blood pressure EFEMP2 gene ERCC6 gene European FAM167A gene FBN1 gene FTO gene GABRB1 gene GATA4 gene gene gene alcohol interaction gene interaction gene linkage disequilibrium gene locus gene replication genetic association genetic trait genetics genome-wide association study GRK5 gene health status heart arrhythmia heart failure heart hypertrophy Hispanic human KCNJ11 gene major clinical study MAPKAPK2 gene mean arterial pressure MTHFR gene multi ancestry NOS3 gene NPPA gene pathogenesis PINX1 gene protein protein interaction pulse pressure quantitative trait locus single nucleotide polymorphism systolic blood pressure transcription regulation adolescent aged drinking behavior female genetic predisposition genotype environment interaction hypertension male meta analysis middle aged pedigree statistics and numerical data very elderly young adult Aged, 80 and over Alcohol Drinking Cohort Studies Continental Population Groups Gene-Environment Interaction Genetic Predisposition to Disease Humans Polymorphism, Single Nucleotide
Subjects: WG Cardiovascular System
QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 20 May 2020 05:33
Last Modified: 20 May 2020 05:33

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