Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

Abstract

Background: Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45-75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597).

Results: Minor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only.

Conclusion: These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.

Figure 1

Differences in protective (upper panel) or risk (lower panel) minor allele frequency in Puerto Rican versus non-Hispanic whites, by SNP. Tables describe the associated phenotypes for those SNPs with significantly different MAF between populations. *Significantly different MAF between populations, p < 0.0005 Abbreviations: MAF: minor allele frequency; HDL-C: high density lipoprotein; T2DM: type 2 diabetes mellitus; HOMA-IR: homeostasis model assessment of insulin resistance; CAD: coronary artery disease; BMI: body mass index; TG: triglycerides; LDL-C: low density lipoprotein; VLDL-C: very low density lipoprotein; TC: total cholesterol; IHD: ischemic heart disease; CHD: coronary heart disease; HbA1c: glycosylated hemoglobin.

Figure 2

F_ST range (filled circle) for Puerto Ricans (a) and non-Hispanic whites (b) by SNP function. Open squares represent mean F_ST and bars represent three standard deviations from the mean for each SNP function.