Assessment of the potential role of natural selection in type 2 diabetes and related traits across human continental anc
- PDF / 1,146,417 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 78 Downloads / 136 Views
ARTICLE
Assessment of the potential role of natural selection in type 2 diabetes and related traits across human continental ancestry groups: comparison of phenotypic with genotypic divergence Robert L. Hanson 1 & Cristopher V. Van Hout 2 & Wen-Chi Hsueh 1 & Alan R. Shuldiner 2 & Sayuko Kobes 1 & Madhumita Sinha 1 & Leslie J. Baier 1 & Regeneron Genetics Center 2 & William C. Knowler 1 Received: 29 February 2020 / Accepted: 22 July 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
Abstract Aims/hypothesis Prevalence of type 2 diabetes differs among human ancestry groups, and many hypotheses invoke differential natural selection to account for these differences. We sought to assess the potential role of differential natural selection across major continental ancestry groups for diabetes and related traits, by comparison of genetic and phenotypic differences. Methods This was a cross-sectional comparison among 734 individuals from an urban sample (none of whom was more closely related to another than third-degree relatives), including 83 African Americans, 523 American Indians and 128 European Americans. Participants were not recruited based on diabetes status or other traits. BMI was calculated, and diabetes was diagnosed by a 75 g oral glucose tolerance test. In those with normal glucose tolerance (n = 434), fasting insulin and 30 min post-load insulin, adjusted for 30 min glucose, were taken as measures of insulin resistance and secretion, respectively. Whole exome sequencing was performed, resulting in 97,388 common (minor allele frequency ≥ 5%) variants; the coancestry coefficient (FST) was calculated across all markers as a measure of genetic divergence among ancestry groups. The phenotypic divergence index (PST) was also calculated from the phenotypic differences and heritability (which was estimated from genetic relatedness calculated empirically across all markers in 761 American Indian participants prior to the exclusion of close relatives). Under evolutionary neutrality, the expectation is PST = FST, while for traits under differential selection PST is expected to be significantly greater than FST. A bootstrap procedure was used to test the hypothesis PST = FST. Results With adjustment for age and sex, prevalence of type 2 diabetes was 34.0% in American Indians, 12.4% in African Americans and 10.4% in European Americans (p = 2.9 × 10−10 for difference among groups). Mean BMI was 36.3, 33.4 and 33.0 kg/m2, respectively (p = 1.9 × 10−7). Mean fasting insulin was 63.8, 48.4 and 45.2 pmol/l (p = 9.2 × 10−5), while mean 30 min insulin was 559.8, 553.5 and 358.8 pmol/l, respectively (p = 5.7 × 10−8). FST across all markers was 0.130, while PST for liability to diabetes, adjusted for age and sex, was 0.149 (p = 0.35 for difference with FST). PST was 0.094 for BMI (p = 0.54), 0.095 for fasting insulin (p = 0.54) and 0.216 (p = 0.18) for 30 min insulin. For type 2 diabetes and BMI, the maximum divergence between populations was observ
Data Loading...
