Genetic admixture, adipocytokines, and adiposity in Black Americans: the Health, Aging, and Body Composition study

Abstract

Adipocytokines are a subset of cytokines produced by adipose tissue and are associated with risk of type II diabetes and atherosclerosis. Levels of adipocytokines differ between Black and White Americans, even after adjustment for differences in adiposity, diseases associated with adipocytokines including type 2 diabetes and cardiovascular disease, and general socioeconomic status indicators such as income. We used a series of ancestry informative markers to estimate genetic ancestry in a population-based study of older Black Americans, and examined the association between genetic ancestry and adipocytokines and soluble receptors to help determine which of these may be most amenable to admixture mapping. We typed 35 ancestry informative markers in 1,241 self-reported Black Americans with available DNA from the Health, Aging, and Body Composition (Health ABC) study with available DNA and used a maximum likelihood approach to estimate percent European ancestry. We used linear regression models to determine the association between these adipocytokines and percent ancestry, and staged models to examine whether adiposity or other measures affected the associations of genetic ancestry and adipocytokines. Mean European ancestry was 22.3+/-15.9%. In multivariate adjusted models, the strongest associations observed were between higher European ancestry and interleukin-6 soluble receptor (IL-6 SR), C-reactive protein (CRP), and adiponectin levels, with interleukin-2 soluble receptor (IL-2 SR) and soluble tumor necrosis factor receptor II (TNF-alpha SR II) also showing more modest but significant associations. The association with adiponectin became stronger after adjustment for adiposity. These novel findings suggest that admixture mapping may identify genetic factors influencing the levels of IL-6 SR, CRP, IL-2 SR, and adiponectin.

Comparing Genetic Ancestry and Self-Described Race in African Americans Born in the United States and in Africa

“…The African American cohort in our study had a mean of 15% European admixture, which is consistent with previous reports of a range of 7% to 23% European admixture among U.S. African Americans (14)(15)(16). Of note, the estimates of 4% European and 1% Native American ancestry in the Nigerian population is likely due to bias in MLE due to the limited number of markers.…”

“…Genetic studies have shown that African Americans form a diverse group with percent European admixture estimated to range between 7% and 23% (14)(15)(16). Genotyping of self-identified African Americans participating in the Cardiovascular Health Study revealed that among self-reported Africans there are differences in genetic ancestry that are correlated with some clinically important endpoints (15).…”

Meta-Analysis of Genome-Wide Association Studies Identifies Genetic Risk Factors for Stroke in African Americans

“…COMPASS includes cohort studies–Atherosclerosis Risk in Communities (ARIC) Study 15 , Cardiovascular Health Study (CHS) 16 , Dynamics of Health, Aging and Body Composition Study (HABC) 17 , and the Women’s Health Initiative (WHI) 18 ,–and case-control studies–Genetics of Early Onset Stroke (GEOS) 19 , Ischemic Stroke Genetics Study (ISGS) 20 , Vitamin Intervention for Stroke Prevention (VISP) 21 and Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) 22 , –as well as an affected sibpair study–Siblings with Ischemic Stroke Study (SWISS) 23 .…”

Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease

“…Subjects were well functioning men and women aged 70–79 years sampled from Medicare beneficiaries living in or around Alleghany County, Pennsylvania and Memphis, Tennessee. Inclusion and exclusion criteria have been described in detail elsewhere 27. Of a sample of 3075 subjects, 1281 were self reported African Americans.…”