Genetic Loci and Novel Discrimination Measures Associated with Blood Pressure Variation in African Americans Living in Tallahassee

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.

Shortened telomere length is associated with unfair treatment attributed to race in African Americans living in Tallahassee, Florida

“…UT‐Self did not associate with TL, prompting the interpretation that only unfair treatment attributed to race is processed in a pathway that leads to shortened TL. Neither of the UT‐Other measures associated with TL, although we previously found associations of UT‐Other and UT‐Self with blood pressure through different biological pathways (Boulter et al, ; Quinlan et al, ). Specifically, in Quinlan et al (), UT‐Self associated with BP through interactions with genetic variants involved in cardiovascular disease and UT‐Other associated with BP through interactions with genetic variants involved in mental health.…”

“…Neither of the UT‐Other measures associated with TL, although we previously found associations of UT‐Other and UT‐Self with blood pressure through different biological pathways (Boulter et al, ; Quinlan et al, ). Specifically, in Quinlan et al (), UT‐Self associated with BP through interactions with genetic variants involved in cardiovascular disease and UT‐Other associated with BP through interactions with genetic variants involved in mental health. The meaning and impact of unfair treatment may vary across dimensions like Self vs Other and Race‐related vs general, and these differences may explain why we only find an association between TL and UT‐Race‐Self.…”

“…While we cannot say if UT‐Other, UT‐Race‐Self, and UT‐Race‐Other can be applied more broadly to African American communities outside of Tallahassee, we can stress the importance of active participant engagement in the development of these measures. In addition to TL, we have reported associations between our ethnographically informed, modified UT measures and blood pressure through interactions with genetic markers involved in both cardiovascular disease and mental health (Boulter et al, ; Quinlan et al, ). As such, we encourage other research groups to adopt a community‐based participatory framework on both ethical and empirical grounds (Gravlee et al, ; Israel, Schulz, Parker, & Becker, ).…”

“…The adverse effects of perceived threats or maltreatment of others in a shared environment has mostly been studied in children (eg, Kelly, Becares, & Nazroo, ; Priest, Paradies, Stevens, & Bailie, ). Our research team developed a measure of vicarious discrimination while working with the same Tallahassee cohort as in the current study; we found that experiences of vicarious racism were associated with blood pressure through interactions with genetic markers involved in both cardiovascular disease and mental health (Boulter et al, ; Quinlan et al, ). As such, vicarious racism is an important stressor to include in investigations of racial inequalities.…”

Human races are not like dog breeds: refuting a racist analogy

“…Rather, racial experience is emphasized as an embodied experience that is as real and as valid as biological variation. " Racism can have damaging consequences on human health and well-being (Gravlee 2009;Gravlee et al 2009;Sims et al 2012;Boulter et al 2015;Quinlan et al 2016). Yudell et al (2016) wrote that they "acknowledge that using race as a political or social category to study racism and its biological effects, although fraught with challenges, remains necessary.…”