Admixture mapping identifies genetic regions associated with blood pressure phenotypes in African Americans

Abstract

Hypertension occurs at a higher rate in African Americans than in European Americans. Based on the assumption that causal variants are more frequently found on DNA segments inherited from the ancestral population with higher disease risk, we employed admixture mapping to identify genetic loci with excess local African ancestry associated with blood pressure. Chromosomal regions 1q21.2-21.3, 4p15.1, 19q12 and 20p13 were significantly associated with diastolic blood pressure (β = 5.28,-7.94,-6.82 and 5.89, P-value = 6.39E-04, 2.07E-04, 6.56E-05 and 5.04E-04, respectively); 1q21.2-21.3 and 19q12 were also significantly associated with mean arterial pressure (β = 5.86 and-6.40, P-value = 5.32E-04 and 6.37E-04, respectively). We further selected SNPs that had large allele frequency differences within these regions and tested their association with blood pressure. SNP rs4815428 was significantly associated with diastolic blood pressure after Bonferroni correction (β =-2.42, P-value = 9.57E-04), and it partially explained the admixture mapping signal at 20p13. SNPs rs771205 (β =-1.99, P-value = 3.37E-03), rs3126067, rs2184953 and rs58001094 (the latter three exhibit strong linkage disequilibrium, β =-2.3, P-value = 1.4E-03) were identified to be significantly associated with mean arterial pressure, and together they fully explained the admixture signal at 1q21.2-21.3. Although no SNP at 4p15.1 showed large ancestral allele frequency differences in our dataset, we detected association at low-frequency African-specific variants that mapped predominantly to the gene PCDH7, which is most highly expressed in aorta. Our results suggest that these regions may harbor genetic variants that contribute to the different prevalence of hypertension.

Genome-wide Association Study Meta-analysis of Blood Pressure Traits and Hypertension in Sub-Saharan African Populations: An AWI-Gen Study

“…There is a need for larger GWAS of continental African populations, to better investigate the role of these SNPs in BP regulation among Africans. Similar to this study, genetic associations linked with BP-related traits in African populations have been found to be limited to those populations 25,26,47,48 .…”

Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape

“…Although most multi-ancestry genome-wide mapping efforts to date have been limited to GWAS meta-analysis [119][120][121][122] or admixture mapping [123][124][125][126][127] , several works have intensively explored the idea of a joint multi-ancestry GWAS [37][38][39]128,129 . In general, those works have agreed that adjustment for global genomic ancestry is necessary to avoid spurious results and that adjustment for local genomic ancestry is useful for obtaining more accurate effect sizes and better signal localization in the presence of LD expansion that comes with admixture 130 .…”

Joint Multi-Ancestry and Admixed GWAS Reveals the Complex Genetics behind Human Cranial Vault Shape

“…Although most multi-ancestry genome-wide mapping efforts to date have been limited to GWAS meta-analysis [115][116][117][118] or admixture mapping [119][120][121][122][123] , several works have intensively explored the idea of a joint multi-ancestry GWAS [35][36][37]124,125 . In general, those works have agreed that adjustment for global genomic ancestry is necessary to avoid spurious results and that adjustment for local genomic ancestry is useful for obtaining more accurate effect sizes and better signal localization in the presence of LD expansion that comes with admixture 126 .…”