Key result
Of 37 known European and Asian type 2 diabetes risk alleles, only two SNPs in TCF7L2 were associated with type 2 diabetes in the Qatari population.
Why the study?
Do known European and Asian T2D risk alleles confer risk for T2D in the Qatari population?
Case-Control (n=1,714)
Do known European and Asian T2D risk alleles confer risk for T2D in the Qatari population?
Known European and Asian T2D risk alleles do not significantly contribute to the high prevalence of T2D in the Qatari population, suggesting distinct genetic risk factors in this group.
Answers are grounded in this paper and cite their sources.
European/Asian T2D risk alleles show limited transferability to Qataris; challenges polygenic score applicability and leaves open ancestry-specific discovery.
BACKGROUND: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. METHODS: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. RESULTS: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. CONCLUSIONS: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.
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O’Beirne et al. (2016) conducted a case-control in Type 2 Diabetes (n=1,714). Known European/Asian T2D risk alleles (37 SNPs) vs. Controls without T2D was evaluated on Association of rs7903146 (TCF7L2) with Type 2 Diabetes (OR 1.36, 95% CI 1.146-1.618, p=0.029). Of 37 known European and Asian type 2 diabetes risk alleles, only two SNPs in TCF7L2 were associated with type 2 diabetes in the Qatari population.
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