Abstract
Sequencing of the human genome and decades of genetic association and linkage studies have dramatically improved our understanding of the etiology of many diseases. However, the multiple causes of complex diseases are still not well understood, in part because genetic and sociocultural risk factors are not typically investigated concurrently. Hypertension is a leading risk factor for cardiovascular disease and afflicts more African Americans than any other racially defined group in the US. Few genetic loci for hypertension have been replicated across populations, which may reflect population-specific differences in genetic variants and/or inattention to relevant sociocultural factors. Discrimination is a salient sociocultural risk factor for poor health and has been associated with hypertension. Here we use a biocultural approach to study blood pressure (BP) variation in African Americans living in Tallahassee, Florida by genotyping over 30,000 single nucleotide polymorphisms (SNPs) and capturing experiences of discrimination using novel measures of unfair treatment of self and others (n = 157). We perform a joint admixture and genetic association analysis for BP that prioritizes regions of the genome with African ancestry. We only report significant SNPs that were confirmed through our simulation analyses, which were performed to determine the false positive rate. We identify eight significant SNPs in five genes that were previously associated with cardiovascular diseases. When we include measures of unfair treatment and test for interactions between SNPs and unfair treatment, we identify a new class of genes involved in multiple phenotypes including psychosocial distress and mood disorders. Our results suggest that inclusion of culturally relevant stress measures, like unfair treatment in African Americans, may reveal new genes and biological pathways relevant to the etiology of hypertension, and may also improve our understanding of the complexity of gene-environment interactions that underlie complex diseases.
Highlights
African Americans bear a disproportionate burden of ill health in the United States (US) [1] with cardiovascular disease being the leading contributor to reduced life expectancy
The lack of replication of genetic loci associated with blood pressure (BP) across populations of different ancestries has generally been attributed to population-specific genetic variants, variation in allele frequencies, different patterns of linkage disequilibrium (LD) across populations or low statistical power due to limited sample size, in African-Americans [15]
We assay over 30,000 genetic markers [ancestry informative markers (AIMs) and single nucleotide polymorphisms (SNPs) in genes associated with hypertension, cardiovascular disease, and stress] and include new measures of unfair treatment in order to develop an expanded picture of risk factors underlying BP variation
Summary
African Americans bear a disproportionate burden of ill health in the United States (US) [1] with cardiovascular disease being the leading contributor to reduced life expectancy. The lack of replication of genetic loci associated with BP across populations of different ancestries has generally been attributed to population-specific genetic variants, variation in allele frequencies, different patterns of linkage disequilibrium (LD) across populations or low statistical power due to limited sample size, in African-Americans [15]. BP levels vary widely across populations, with the prevalence of hypertension lowest in populations with low levels of environmental and psychological stress and extensive genetic variability [18], suggesting that the major determinants of high BP are likely to be a constellation of sociocultural factors, with genetic determination being limited to variation within populations and to interactions with the environment [18]. We assay over 30,000 genetic markers [ancestry informative markers (AIMs) and SNPs in genes associated with hypertension, cardiovascular disease, and stress] and include new measures of unfair treatment in order to develop an expanded picture of risk factors underlying BP variation
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.