Combined effects of 17 common genetic variants on type 2 diabetes risk in a Han Chinese population

Qibin Qi, H. Li, Y. Wu, C. Liu, H. Wu, Z. Yu, L. Qi, F. B. Hu, R. J F Loos, X. Lin

Research output: Contribution to journalArticle

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Abstract

Aims/hypothesis The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese. Methods We genotyped17variantsin17lociina population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve. Results The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12-1.23, p = 1.3x 10-12) and 1.12 (95% CI 1.091.16, p=7.5 x10-14), respectively. Compared with participants with GRS ≤11.0 (7.63%), those with GRS ≥19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49-8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function (p=8.4 x10-10). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA1c levels (p=0.04 and p=0.03 for interaction, respectively). Discrimination of diabetes risk was improved (p<0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added. Conclusions/interpretation In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)2163-2166
Number of pages4
JournalDiabetologia
Volume53
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Fingerprint

Type 2 Diabetes Mellitus
Population
Aptitude
Genome-Wide Association Study
Population Genetics
ROC Curve
Hyperglycemia
Area Under Curve
Fasting
Alleles
Odds Ratio
Glucose

Keywords

  • Chinese
  • Genetic risk score
  • Genetic variants
  • Population-based study
  • Receiver operating characteristic
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Combined effects of 17 common genetic variants on type 2 diabetes risk in a Han Chinese population. / Qi, Qibin; Li, H.; Wu, Y.; Liu, C.; Wu, H.; Yu, Z.; Qi, L.; Hu, F. B.; Loos, R. J F; Lin, X.

In: Diabetologia, Vol. 53, No. 10, 10.2010, p. 2163-2166.

Research output: Contribution to journalArticle

Qi, Q, Li, H, Wu, Y, Liu, C, Wu, H, Yu, Z, Qi, L, Hu, FB, Loos, RJF & Lin, X 2010, 'Combined effects of 17 common genetic variants on type 2 diabetes risk in a Han Chinese population', Diabetologia, vol. 53, no. 10, pp. 2163-2166. https://doi.org/10.1007/s00125-010-1826-5
Qi, Qibin ; Li, H. ; Wu, Y. ; Liu, C. ; Wu, H. ; Yu, Z. ; Qi, L. ; Hu, F. B. ; Loos, R. J F ; Lin, X. / Combined effects of 17 common genetic variants on type 2 diabetes risk in a Han Chinese population. In: Diabetologia. 2010 ; Vol. 53, No. 10. pp. 2163-2166.
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AU - Qi, Qibin

AU - Li, H.

AU - Wu, Y.

AU - Liu, C.

AU - Wu, H.

AU - Yu, Z.

AU - Qi, L.

AU - Hu, F. B.

AU - Loos, R. J F

AU - Lin, X.

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N2 - Aims/hypothesis The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese. Methods We genotyped17variantsin17lociina population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve. Results The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12-1.23, p = 1.3x 10-12) and 1.12 (95% CI 1.091.16, p=7.5 x10-14), respectively. Compared with participants with GRS ≤11.0 (7.63%), those with GRS ≥19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49-8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function (p=8.4 x10-10). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA1c levels (p=0.04 and p=0.03 for interaction, respectively). Discrimination of diabetes risk was improved (p<0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added. Conclusions/interpretation In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes.

AB - Aims/hypothesis The recent advent of genome-wide association studies has considerably accelerated the identification of type 2 diabetes loci. We aimed to investigate the combined effects of multiple genetic variants, alone or in combination with conventional risk factors, on type 2 diabetes and diabetes-related traits in Han Chinese. Methods We genotyped17variantsin17lociina population-based Han Chinese cohort including 3,210 unrelated individuals. A genetic risk score (GRS) was calculated on the basis of these variants. The discriminatory ability was assessed by the area under the receiver operating characteristics curve. Results The odds ratio for type 2 diabetes and hyperglycaemia with each GRS point (per risk allele) was 1.18 (95% CI 1.12-1.23, p = 1.3x 10-12) and 1.12 (95% CI 1.091.16, p=7.5 x10-14), respectively. Compared with participants with GRS ≤11.0 (7.63%), those with GRS ≥19.0 (8.87%) had a 4.58-fold higher risk (95% CI 2.49-8.42) of type 2 diabetes. The GRS also showed a significant association with lower beta cell function estimated by HOMA of beta cell function (p=8.4 x10-10). In addition, we observed significant interactive effects between GRS and BMI on fasting glucose and HbA1c levels (p=0.04 and p=0.03 for interaction, respectively). Discrimination of diabetes risk was improved (p<0.001) when the GRS was added to a model including clinical risk factors. The AUCs were 0.62 and 0.77, respectively, for the GRS and conventional clinic risk factors alone, and 0.79 when the GRS was added. Conclusions/interpretation In this Han Chinese population, the GRS of 17 combined variants modestly but significantly improved discrimination of the conventional risk factors for type 2 diabetes.

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KW - Population-based study

KW - Receiver operating characteristic

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