The genetic structure of the Turkish population reveals high levels of variation and admixture

Abstract

people who live in the five independent Turkic countries in Central Asia, namely Azerbaijan, Turkmenistan, Uzbekistan, Kazakhstan, and Kyrgyzstan. A study investigating the Y haplogroups of Turkish (TR) males revealed that the proportion of recent paternal gene flow from Central Asia was ∼9%, thereby raising the possibility that modern-day Anatolia is an admixture of preexisting Anatolian and Turkic peoples (3). The practice of consanguineous marriage is frequent in Turkey, especially in the eastern provinces (4). This should, in principle, help to facilitate disease gene discovery, as the increased frequency of homozygosity among members of inbred populations has led to the identification of many disease genes (5–8). The genetic admixture and consanguinity have had a significant effect on the genetic diversity of Middle Eastern populations (9, 10). The characterization of the Greater Middle East (GME) Variome, comprising the most comprehensive genomic database for Middle Eastern populations, has shown that knowledge of the genomic architecture of these populations facilitates disease gene identification in family studies and in genome-wide association studies (GWAS) of populations (11). Until now, the GME has been the largest resource representing the genetic variation in Turkey, albeit with only 140 out of a total of 1,111 samples coming from the TR Peninsula. Thus, based on the larger population of Turkey relative to its immediate neighbors, the TR population is underrepresented in current genomic databases. Furthermore, gnomAD, as one of the most comprehensive genetic variation resources, does not contain TR whole-exome sequencing (WES) or whole-genome sequencing (WGS) data (12). Therefore, a comprehensive database of alleles in the TR population should facilitate disease gene identification in consanguineous families and the assessment of the clinical phenotypes of individuals who are homozygous for mutations in specific genes. Finally, most GWAS to date have analyzed DNA from European