Figure 6.

VNTRs with high population divergence are enriched for functional associations with gene expression, methylation, and human traits

We estimated population stratification of VNTR copy number with the V_ST statistic in samples from the Human Genome Diversity Panel. Both eVNTRs and mVNTRs were enriched for VNTRs with high V_ST, and consistent with the notion that selection may have acted to modify copy number of functional VNTR loci in specific populations, we also observed that eVNTRs with elevated V_ST were enriched for putative phenotype associations. Shown are six example VNTRs with high V_ST.

(A) A 40-mer VNTR (chr12: 499,333–499,718, hg38) expanded in the Oceanic population.

(B) A 33-mer VNTR (chr21: 27,626,691–27,627,440, hg38) expanded in Asians.

(C) A 20-mer VNTR (chr2: 220,823,510–220,823,980, hg38) expanded in Americans.

(D) An 81-mer VNTR (chr2: 241,457,351–241,457,836, hg38) expanded in Americans is associated with expression level of SEPT2 (MIM: 601506) in skin and thyroid and is potentially linked to multiple human traits by GWASs.

(E) A 24-mer VNTR (chr20: 62,825,064–62,825,209, hg38) expanded in East Asians is associated with expression level of COL9A3 (MIM: 120270) in adipose tissue, muscle, and blood.

(F) A 39-mer VNTR (chr19: 3,177,632–3,178,287, hg38) expanded in East Asians is associated with expression level of S1PR4 (MIM: 603751) in mammary tissue, thyroid, and esophagus.