Dataset Information

Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

ABSTRACT: Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region (p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region (p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

SUBMITTER: Smith JA

PROVIDER: S-EPMC5751013 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

Smith Jennifer A JA Zhao Wei W Yasutake Kalyn K August Carmella C Ratliff Scott M SM Faul Jessica D JD Boerwinkle Eric E Chakravarti Aravinda A Diez Roux Ana V AV Gao Yan Y Griswold Michael E ME Heiss Gerardo G Kardia Sharon L R SLR Morrison Alanna C AC Musani Solomon K SK Mwasongwe Stanford S North Kari E KE Rose Kathryn M KM Sims Mario M Sun Yan V YV Weir David R DR Needham Belinda L BL

International journal of environmental research and public health 20171218 12

Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), ...[more]

PMID: 29258278

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Project description:BACKGROUND/OBJECTIVES:Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition. SUBJECTS/METHODS:To identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15?945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants. RESULTS:Of the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses. CONCLUSIONS:Of 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.

Project description:Background: Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. Methods: We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Results: Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. Discussion: The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. Other relevant information: SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).

Dataset Information

Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

Publications

Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

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