Genetic Substructure of Kuwaiti Population Reveals Migration History

Abstract

The State of Kuwait is characterized by settlers from Saudi Arabia, Iran, and other regions of the Arabian Peninsula. The settlements and subsequent admixtures have shaped the genetics of Kuwait. High prevalence of recessive disorders and metabolic syndromes (that increase risk of diabetes) is seen in the peninsula. Understanding the genetic structure of its population will aid studies designed to decipher the underlying causes of these disorders. In this study, we analyzed 572,366 SNP markers from 273 Kuwaiti natives genotyped using the illumina HumanOmniExpress BeadChip. Model-based clustering identified three genetic subgroups with different levels of admixture. A high level of concordance (Mantel test, p=0.0001 for 9999 repeats) was observed between the derived genetic clusters and the surname-based ancestries. Use of Human Genome Diversity Project (HGDP) data to understand admixtures in each group reveals the following: the first group (Kuwait P) is largely of West Asian ancestry, representing Persians with European admixture; the second group (Kuwait S) is predominantly of city-dwelling Saudi Arabian tribe ancestry, and the third group (Kuwait B) includes most of the tent-dwelling Bedouin surnames and is characterized by the presence of 17% African ancestry. Identity by Descent and Homozygosity analyses find Kuwait’s population to be heterogeneous (placed between populations that have large amount of ROH and the ones with low ROH) with Kuwait S as highly endogamous, and Kuwait B as diverse. Population differentiation FST estimates place Kuwait P near Asian populations, Kuwait S near Negev Bedouin tribes, and Kuwait B near the Mozabite population. FST distances between the groups are in the range of 0.005 to 0.008; distances of this magnitude are known to cause false positives in disease association studies. Results of analysis for genetic features such as linkage disequilibrium decay patterns conform to Kuwait’s geographical location at the nexus of Africa, Europe, and Asia.

Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population

“…An overwhelming proportion (63%) of the disorders documented in the Catalogue for Transmission Genetics in Arabs (CTGA) follows a recessive mode of inheritance. A great burden of recessive alleles and homozygosity in Kuwaiti population has been reported in our publications (33) and in our ongoing studies (Under Review elsewhere; John SE., Antony D., Eaaswarkhanth M., Hebbar P., Channanath AM., Thomas D., Devarajan S., Tuomilehto J., Osama Alsmadi O., Thanaraj TA.…”

“…Bedouins with a characteristic presence of 17% African ancestry (33). The population of Kuwait, like other states in the Peninsula, has been practicing consanguineous marriages (involving first or second cousins or relatives within the large family or the same tribe); the rate of consanguineous marriages can be as high as 54.3% (34).…”

Association of the insertion allele of the common ACE gene polymorphism with type 2 diabetes mellitus among Kuwaiti cardiovascular disease patients

“…However, three genetic subgroups have been previously defined in the Kuwaiti population, and therefore future studies may need to be stratified accordingly. 25,26 Our association of the ACE I allele with T2DM can be explained by understanding the complexity of the renninangiotensin-aldosterone system (RAAS) as reviewed by Rahimi et al 27 Angiotensin II is converted by ACE, resulting in aldosterone secretion and elevated blood pressure. 27 A study using intravenous infusion of angiotensin II showed an enhanced blood flow resulting in insulin sensitivity.…”

Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

“…Previous analyses of the populations of the Arabian Peninsula (Hunter-Zinck et al 2010;Alsmadi et al 2013) have found three distinct clusters that reflect primary ancestry: Q1 (Bedouin); Q2 (Persian-South Asian); and Q3 (African) (Omberg et al 2012). By assessment of medical records and ancestry-informative SNP genotyping (Supplemental Fig.…”

“…Although there have been many analyses of Chr Y and mtDNA sampled from Arab individuals (Abu-Amero et al 2007Rowold et al 2007), and there have been previous surveys of genetic variation of people within the peninsula and immediately surrounding regions conducted with genotyping arrays (Behar et al 2010;HunterZinck et al 2010;Alsmadi et al 2013;Markus et al 2014;Shriner et al 2014) and deep exome sequencing (Rodriguez-Flores et al 2012, 2014Alsmadi et al 2014), and by individual high-coverage genomes (Alsmadi et al 2014;John et al 2015), the sample of rare and common genetic variation throughout the genome in our sample provides a far more complete picture of how both ancient and recent migration events have contributed to the genetics of the modern peoples of the Arabian Peninsula. For understanding how human migration history has determined the structure of modern genomes, our identification of a cluster of Q1 (Bedouin) as the most distant ancestors of non-Africans is of considerable interest, particularly given the suspected route of migration out of Africa and into the surrounding continents.…”