Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.pdf (3.03 MB)
Download file

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

Download (3.03 MB)
journal contribution
posted on 21.08.2018, 08:51 by MF Feitosa, AT Kraja, DI Chasman, YJ Sung, TW Winkler, I Ntalla, X Guo, N Franceschini, C-Y Cheng, X Sim, D Vojinovic, J Marten, SK Musani, C Li, AR Bentley, MR Brown, K Schwander, MA Richard, R Noordam, H Aschard, TM Bartz, LF Bielak, R Dorajoo, V Fisher, FP Hartwig, ARVR Horimoto, KK Lohman, AK Manning, T Rankinen, AV Smith, SM Tajuddin, MK Wojczynski, M Alver, M Boissel, Q Cai, A Campbell, JF Chai, X Chen, J Divers, C Gao, A Goel, Y Hagemeijer, SE Harris, M He, F-C Hsu, AU Jackson, M Kähönen, A Kasturiratne, P Komulainen, B Kühnel, F Laguzzi, J Luan, N Matoba, IM Nolte, S Padmanabhan, M Riaz, R Rueedi, A Robino, MA Said, RA Scott, T Sofer, A Stančáková, F Takeuchi, BO Tayo, PJ van der Most, TV Varga, V Vitart, Y Wang, EB Ware, HR Warren, S Weiss, W Wen, LR Yanek, W Zhang, JH Zhao, S Afaq, N Amin, M Amini, DE Arking, T Aung, E Boerwinkle, I Borecki, U Broeckel, M Brown, M Brumat, GL Burke, M Canouil, A Chakravarti, S Charumathi, Y-D Ida Chen, JM Connell, A Correa, L de Las Fuentes, R de Mutsert, HJ de Silva, X Deng, J Ding, Q Duan, CB Eaton, G Ehret, RN Eppinga, E Evangelou, JD Faul, SB Felix, NG Forouhi, T Forrester, OH Franco, Y Friedlander, I Gandin, H Gao, M Ghanbari, B Gigante, CC Gu, D Gu, SP Hagenaars, G Hallmans, TB Harris, J He, S Heikkinen, C-K Heng, M Hirata, BV Howard, MA Ikram, InterAct Consortium, U John, T Katsuya, CC Khor, TO Kilpeläinen, W-P Koh, JE Krieger, SB Kritchevsky, M Kubo, J Kuusisto, TA Lakka, CD Langefeld, C Langenberg, LJ Launer, B Lehne, CE Lewis, Y Li, S Lin, J Liu, M Loh, T Louie, R Mägi, CA McKenzie, T Meitinger, A Metspalu, Y Milaneschi, L Milani, KL Mohlke, Y Momozawa, MA Nalls, CP Nelson, N Sotoodehnia, JM Norris, JR O'Connell, ND Palmer, T Perls, NL Pedersen, A Peters, PA Peyser, N Poulter, LJ Raffel, OT Raitakari, K Roll, LM Rose, FR Rosendaal, JI Rotter, CO Schmidt, PJ Schreiner, N Schupf, WR Scott, PS Sever, Y Shi, S Sidney, M Sims, CM Sitlani, JA Smith, H Snieder, JM Starr, K Strauch, HM Stringham, NYQ Tan, H Tang, KD Taylor, YY Teo, YC Tham, ST Turner, AG Uitterlinden, P Vollenweider, M Waldenberger, L Wang, YX Wang, WB Wei, C Williams, J Yao, C Yu, J-M Yuan, W Zhao, AB Zonderman, DM Becker, M Boehnke, DW Bowden, JC Chambers, IJ Deary, T Esko, M Farrall, PW Franks, BI Freedman, P Froguel, P Gasparini, C Gieger, JB Jonas, Y Kamatani, N Kato, JS Kooner, Z Kutalik, M Laakso, CC Laurie, K Leander, T Lehtimäki, LC Study, PKE Magnusson, AJ Oldehinkel, BWJH Penninx, O Polasek, DJ Porteous, R Rauramaa, NJ Samani, J Scott, X-O Shu, P van der Harst, LE Wagenknecht, NJ Wareham, H Watkins, DR Weir, AR Wickremasinghe, T Wu, W Zheng, C Bouchard, K Christensen, MK Evans, V Gudnason, BL Horta, SLR Kardia, Y Liu, AC Pereira, BM Psaty, PM Ridker, RM van Dam, WJ Gauderman, X Zhu, DO Mook-Kanamori, M Fornage, CN Rotimi, LA Cupples, TN Kelly, ER Fox, C Hayward, CM van Duijn, ES Tai, TY Wong, C Kooperberg, W Palmas, K Rice, AC Morrison, P Elliott, MJ Caulfield, PB Munroe, DC Rao, MA Province, D Levy
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.

Funding

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

History

Citation

PLoS ONE, 2018, 13(6): e0198166.

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

PLoS ONE

Publisher

Public Library of Science

eissn

1932-6203

Acceptance date

15/05/2018

Available date

21/08/2018

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198166

Notes

The meta-analysis results from this study are available at dbGAP (accession number phs000930).

Language

en

Usage metrics

Categories

Keywords

Exports