Dataset Information

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 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.

SUBMITTER: Feitosa MF

PROVIDER: S-EPMC6005576 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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 MF Kraja Aldi T AT Chasman Daniel I DI Sung Yun J YJ Winkler Thomas W TW Ntalla Ioanna I Guo Xiuqing X Franceschini Nora N Cheng Ching-Yu CY Sim Xueling X Vojinovic Dina D Marten Jonathan J Musani Solomon K SK Li Changwei C Bentley Amy R AR Brown Michael R MR Schwander Karen K Richard Melissa A MA Noordam Raymond R Aschard Hugues H Bartz Traci M TM Bielak Lawrence F LF Dorajoo Rajkumar R Fisher Virginia V Hartwig Fernando P FP Horimoto Andrea R V R ARVR Lohman Kurt K KK Manning Alisa K AK Rankinen Tuomo T Smith Albert V AV Tajuddin Salman M SM Wojczynski Mary K MK Alver Maris M Boissel Mathilde M Cai Qiuyin Q Campbell Archie A Chai Jin Fang JF Chen Xu X Divers Jasmin J Gao Chuan C Goel Anuj A Hagemeijer Yanick Y Harris Sarah E SE He Meian M Hsu Fang-Chi FC Jackson Anne U AU Kähönen Mika M Kasturiratne Anuradhani A Komulainen Pirjo P Kühnel Brigitte B Laguzzi Federica F Luan Jian'an J Matoba Nana N Nolte Ilja M IM Padmanabhan Sandosh S Riaz Muhammad M Rueedi Rico R Robino Antonietta A Said M Abdullah MA Scott Robert A RA Sofer Tamar T Stančáková Alena A Takeuchi Fumihiko F Tayo Bamidele O BO van der Most Peter J PJ Varga Tibor V TV Vitart Veronique V Wang Yajuan Y Ware Erin B EB Warren Helen R HR Weiss Stefan S Wen Wanqing W Yanek Lisa R LR Zhang Weihua W Zhao Jing Hua JH Afaq Saima S Amin Najaf N Amini Marzyeh M Arking Dan E DE Aung Tin T Boerwinkle Eric E Borecki Ingrid I Broeckel Ulrich U Brown Morris M Brumat Marco M Burke Gregory L GL Canouil Mickaël M Chakravarti Aravinda A Charumathi Sabanayagam S Ida Chen Yii-Der YD Connell John M JM Correa Adolfo A de las Fuentes Lisa L de Mutsert Renée R de Silva H Janaka HJ Deng Xuan X Ding Jingzhong J Duan Qing Q Eaton Charles B CB Ehret Georg G Eppinga Ruben N RN Evangelou Evangelos E Faul Jessica D JD Felix Stephan B SB Forouhi Nita G NG Forrester Terrence T Franco Oscar H OH Friedlander Yechiel Y Gandin Ilaria I Gao He H Ghanbari Mohsen M Gigante Bruna B Gu C Charles CC Gu Dongfeng D Hagenaars Saskia P SP Hallmans Göran G Harris Tamara B TB He Jiang J Heikkinen Sami S Heng Chew-Kiat CK Hirata Makoto M Howard Barbara V BV Ikram M Arfan MA John Ulrich U Katsuya Tomohiro T Khor Chiea Chuen CC Kilpeläinen Tuomas O TO Koh Woon-Puay WP Krieger José E JE Kritchevsky Stephen B SB Kubo Michiaki M Kuusisto Johanna J Lakka Timo A TA Langefeld Carl D CD Langenberg Claudia C Launer Lenore J LJ Lehne Benjamin B Lewis Cora E CE Li Yize Y Lin Shiow S Liu Jianjun J Liu Jingmin J Loh Marie M Louie Tin T Mägi Reedik R McKenzie Colin A CA Meitinger Thomas T Metspalu Andres A Milaneschi Yuri Y Milani Lili L Mohlke Karen L KL Momozawa Yukihide Y Nalls Mike A MA Nelson Christopher P CP Sotoodehnia Nona N Norris Jill M JM O'Connell Jeff R JR Palmer Nicholette D ND Perls Thomas T Pedersen Nancy L NL Peters Annette A Peyser Patricia A PA Poulter Neil N Raffel Leslie J LJ Raitakari Olli T OT Roll Kathryn K Rose Lynda M LM Rosendaal Frits R FR Rotter Jerome I JI Schmidt Carsten O CO Schreiner Pamela J PJ Schupf Nicole N Scott William R WR Sever Peter S PS Shi Yuan Y Sidney Stephen S Sims Mario M Sitlani Colleen M CM Smith Jennifer A JA Snieder Harold H Starr John M JM Strauch Konstantin K Stringham Heather M HM Tan Nicholas Y Q NYQ Tang Hua H Taylor Kent D KD Teo Yik Ying YY Tham Yih Chung YC Turner Stephen T ST Uitterlinden André G AG Vollenweider Peter P Waldenberger Melanie M Wang Lihua L Wang Ya Xing YX Wei Wen Bin WB Williams Christine C Yao Jie J Yu Caizheng C Yuan Jian-Min JM Zhao Wei W Zonderman Alan B AB Becker Diane M DM Boehnke Michael M Bowden Donald W DW Chambers John C JC Deary Ian J IJ Esko Tõnu T Farrall Martin M Franks Paul W PW Freedman Barry I BI Froguel Philippe P Gasparini Paolo P Gieger Christian C Jonas Jost Bruno JB Kamatani Yoichiro Y Kato Norihiro N Kooner Jaspal S JS Kutalik Zoltán Z Laakso Markku M Laurie Cathy C CC Leander Karin K Lehtimäki Terho T Study Lifelines Cohort LC Magnusson Patrik K E PKE Oldehinkel Albertine J AJ Penninx Brenda W J H BWJH Polasek Ozren O Porteous David J DJ Rauramaa Rainer R Samani Nilesh J NJ Scott James J Shu Xiao-Ou XO van der Harst Pim P Wagenknecht Lynne E LE Wareham Nicholas J NJ Watkins Hugh H Weir David R DR Wickremasinghe Ananda R AR Wu Tangchun T Zheng Wei W Bouchard Claude C Christensen Kaare K Evans Michele K MK Gudnason Vilmundur V Horta Bernardo L BL Kardia Sharon L R SLR Liu Yongmei Y Pereira Alexandre C AC Psaty Bruce M BM Ridker Paul M PM van Dam Rob M RM Gauderman W James WJ Zhu Xiaofeng X Mook-Kanamori Dennis O DO Fornage Myriam M Rotimi Charles N CN Cupples L Adrienne LA Kelly Tanika N TN Fox Ervin R ER Hayward Caroline C van Duijn Cornelia M CM Tai E Shyong ES Wong Tien Yin TY Kooperberg Charles C Palmas Walter W Rice Kenneth K Morrison Alanna C AC Elliott Paul P Caulfield Mark J MJ Munroe Patricia B PB Rao Dabeeru C DC Province Michael A MA Levy Daniel D

PloS one 20180618 6

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 nucl ...[more]

PMID: 29912962

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Project description:Objectives:To assess the extent of interaction between body mass index (BMI) and triglyceride (TG) level and its effects on blood pressure (BP) in elderly individuals in China. Design:Cross-sectional study. Setting:Data were taken from a cross-sectional study called the China Health and Retirement Longitudinal Study. Participants:The analytic sample included 3629 subjects aged 45 to 96 years. Main Outcome Measurements:Data were obtained from the China Health and Retirement Longitudinal Study, which is a cross-sectional study. Age-adjusted partial Pearson's correlation test was used to compare various characteristics and BP. Adjusted associations were first used as linear regression models, as appropriate. Then, general linear models adjusted for related potential confounders were used to examine the synergistic effects of BMI and TG level on BP. Finally, a binary logistic regression model adjusted for confounding factors was used to examine the association between BMI or TG level and hypertension. Results:Age-adjusted partial Pearson's correlation coefficient showed that the TG level was positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both men and women with BMI < 24.0 kg/m2; however, TG level was positively correlated with DBP in women with BMI ? 24.0 kg/m2 but not with DBP in men with BMI ? 24.0 kg/m2. Multiple linear regression analysis showed that BMI level was significantly and positively associated with both SBP and DBP in men and women with BMI < 24.0 kg/m2, and TG level was significantly and positively associated with SBP in women with BMI < 24.0 kg/m2, independent of other confounding factors. A general linear model analysis with adjustment for confounding factors (age, educational level, marital status, current residence, smoking, eating habits, taking activities, antidiabetic medication, antihypertensive therapy, fasting plasma glucose [FPG], low-density lipoprotein cholesterol [LDL-C], estimated glomerular filtration rate [eGFR], and serum uric acid [SUA]) showed no interaction between BMI and TG level and SBP (men, ? = 0.572, P = 0.845; women, ? = 0.122, P = 0.923) and DBP (men, ? = -0.373, P = 0.810; women, ? = 0.272, P = 0.828). A binary logistic regression model analysis with adjustment for confounding factors (age, educational level, marital status, current residence, smoking, drinking, eating habits, taking activities, major accidental injury, physical activity, history of cardiovascular disease, history of liver disease, antilipidemic medication, antidiabetic medication, antihypertensive therapy, FPG, LDL-C, high-density lipoprotein cholesterol [HDL-C], eGFR, and SUA) showed that overweight and obese men and women were more likely to have hypertension (men: odds ratio [OR] = 1.781, 95% confidence interval [CI] = 1.393-2.277; women: OR = 1.653, 95% CI = 1.330-2.055) and women with high TG were more likely to have hypertension (OR = 1.558, 95% CI = 1.219-1.992). Conclusion:An interactive effect of BMI and TG level on BP was not observed in either men or women; however, independent effects of BMI on BP were observed in both men and women, and an association between TG level and hypertension was observed in women.

Dataset Information

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

Publications

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

Similar Datasets

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