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

Authors

  • Nasser M. Al-Daghri,

    Corresponding author
    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Center of Excellence in Biotechnology Research Centre, King Saud University, Riyadh, Saudi Arabia
    3. Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Saudi Arabia
    • Correspondence: Dr Omar Albagha, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom. Tel. :+44 131 6511022. E-mail: omar.albagha@igmm.ed.ac.uk and Dr Nasser Al-Daghri, Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia. Tel.: +96614675939. E-mail: ndaghri@ksu.edu.sa

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  • Khalid M. Alkharfy,

    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Center of Excellence in Biotechnology Research Centre, King Saud University, Riyadh, Saudi Arabia
    3. Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
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  • Majed S. Alokail,

    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Center of Excellence in Biotechnology Research Centre, King Saud University, Riyadh, Saudi Arabia
    3. Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Saudi Arabia
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  • Amal M. Alenad,

    1. School of Biological Sciences, University of Southampton, Southampton, UK
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  • Omar S. Al-Attas,

    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Center of Excellence in Biotechnology Research Centre, King Saud University, Riyadh, Saudi Arabia
    3. Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Saudi Arabia
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  • Abdul Khader Mohammed,

    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Saudi Arabia
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  • Shaun Sabico,

    1. Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia
    2. Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Saudi Arabia
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  • Omar M. E. Albagha

    Corresponding author
    1. Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    • Correspondence: Dr Omar Albagha, Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom. Tel. :+44 131 6511022. E-mail: omar.albagha@igmm.ed.ac.uk and Dr Nasser Al-Daghri, Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia. Tel.: +96614675939. E-mail: ndaghri@ksu.edu.sa

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Summary

Background

Previous 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.

Methods

Here, 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's highest prevalence of T2D.

Results

Eight 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 = 1·27) compared to that reported in South Asian populations (OR = 1·09; I2 = 65·9). Analysis of risk allele scores (RASs) defined by the 8 loci showed that subjects in the top RAS quintile (n = 480) had 2·5-fold increase in disease risk compared to those in the bottom quintile (n = 480; P = 9·5 × 10−12). RASs were also associated with fasting glucose level (β = 0·12; P = 2·2 × 10−9), but not with BMI (P = 0·19). Analysis of a subgroup of subjects with BMI≤30 resulted in two additional loci (SLC30A8; P = 0·03, HMG20A; P = 0·02) showing significant association with T2D.

Conclusions

We 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.

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