Assessing the contribution of 38 genetic loci to the risk of type 2 diabetes in the Saudi Arabian Population

作者：Al Daghri Nasser M; Alkharfy Khalid M; Alokail Majed S; Alenad Amal M; Al Attas Omar S; Mohammed Abdul Khader; Sabico Shaun; Albagha Omar M E^*

来源：Clinical Endocrinology, 2014, 80(4): 532-537.

DOI：10.1111/cen.12187

BackgroundPrevious genome-wide association studies have identified multiple type 2 diabetes (T2D) genetic risk loci in many populations. However, the contribution of these loci to T2D in the Middle Eastern populations with high T2D prevalence is unknown. %26lt;br%26gt;MethodsHere, we investigated the association of 38 T2D risk loci in the Saudi Arabian population (1166 patients with T2D and 1235 healthy controls), which has one of the world%26apos;s highest prevalence of T2D. %26lt;br%26gt;ResultsEight common genetic variants showed a significant association with T2D in our study population. The effect sizes of these loci were comparable to those previously identified in other populations with the exception of HNF4A, which showed a trend for larger effect size in our study population (OR=127) compared to that reported in South Asian populations (OR=109; I-2=659). Analysis of risk allele scores (RASs) defined by the 8 loci showed that subjects in the top RAS quintile (n=480) had 25-fold increase in disease risk compared to those in the bottom quintile (n=480; P=95x10(-12)). RASs were also associated with fasting glucose level (=012; P=22x10(-9)), but not with BMI (P=019). Analysis of a subgroup of subjects with BMI30 resulted in two additional loci (SLC30A8; P=003, HMG20A; P=002) showing significant association with T2D. %26lt;br%26gt;ConclusionsWe have shown for the first time that variants at WFS1, JAZF1, SLC30A8, CDKN2A/B, TCF7L2, KCNQ1, HMG20A, HNF4A and DUSP9 are associated with T2D in the Saudi population. Our findings also suggest substantial overlap of T2D risk loci across many ethnic groups regardless of disease prevalence.

• 出版日期2014-4