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

Feitosa, Mary F.; Kraja, Aldi T.; Chasman, Daniel I.; Sung, Yun J.; Winkler, Thomas W.; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Cheng, Ching Yu and Sim, Xueling, et al. (2018) In PLoS ONE 13(6).
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 ×... (More)

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.

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1932-6203
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10.1371/journal.pone.0198166
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@article{f6c9eb6b-d0a6-4524-be1b-172813823da1,
  abstract     = {<p>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 &lt; 1.0 × 10<sup>-5</sup>). 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 &lt; 5.0 × 10<sup>-8</sup>). For African ancestry samples, we detected 18 potentially novel BP loci (P &lt; 5.0 × 10<sup>-8</sup>) 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.</p>},
  articleno    = {e0198166},
  author       = {Feitosa, Mary F. and Kraja, Aldi T. and Chasman, Daniel I. and Sung, Yun J. and Winkler, Thomas W. and Ntalla, Ioanna and Guo, Xiuqing and Franceschini, Nora and Cheng, Ching Yu and Sim, Xueling and Vojinovic, Dina and Marten, Jonathan and Musani, Solomon K. and Li, Changwei and Bentley, Amy R. and Brown, Michael R. and Schwander, Karen and Richard, Melissa A. and Noordam, Raymond and Aschard, Hugues and Bartz, Traci M. and Bielak, Lawrence F. and Dorajoo, Rajkumar and Fisher, Virginia and Hartwig, Fernando P. and Horimoto, Andrea R.V.R. and Lohman, Kurt K. and Manning, Alisa K. and Rankinen, Tuomo and Smith, Albert V. and Tajuddin, Salman M. and Wojczynski, Mary K. and Alver, Maris and Boissel, Mathilde and Cai, Qiuyin and Campbell, Archie and Chai, Jin Fang and Chen, Xu and Divers, Jasmin and Gao, Chuan and Goel, Anuj and Hagemeijer, Yanick and Harris, Sarah E. and He, Meian and Hsu, Fang Chi and Jackson, Anne U. and Kähönen, Mika and Kasturiratne, Anuradhani and Varga, Tibor V. and Franks, Paul W. and Rice, Kenneth and Morrison, Alanna C and Elliott, Paul and Caulfield, Mark J. and Munroe, Patricia B. and Rao, Dabeeru C. and Province, Michael A and Levy, Daniel},
  issn         = {1932-6203},
  language     = {eng},
  month        = {06},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries},
  url          = {http://dx.doi.org/10.1371/journal.pone.0198166},
  volume       = {13},
  year         = {2018},
}