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Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese

View Article: PubMed Central - PubMed

ABSTRACT

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility.

No MeSH data available.


Odds ratio (OR) of T2DM according to the wGRS (a) and cGRS (b).
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ijerph-13-00863-f001: Odds ratio (OR) of T2DM according to the wGRS (a) and cGRS (b).

Mentions: To investigate the cumulative effect of the risk alleles on T2DM risk, wGRS and cGRS were calculated for all participants. Four variants inSLC16A11, three in CDKAL1, two in C2CD4A/B, and two in IGF2BP2 were in strong linkage disequilibrium (r2 range from 0.78 to 1.00, Figure S1); therefore four variants in each gene with the highest OR in association analysis together with another 15 variants in 15 genes were used to construct genetic risk scores. The median wGRS was 0.98 (interquartile range (IQR): 0.71) and 0.83 (IQR: 0.46) in T2DM and controls, respectively, while the median cGRS was 15 (IQR: 4) and 14 (IQR: 4) in T2DM and controls, respectively. Both wGRS and cGRS were significantly associated with T2DM susceptibility (AOR = 1.93, 95% CI = 1.42–2.62, p < 0.001; AOR = 1.07, 95% CI = 1.01–1.13, p = 0.030, respectively). In addition, the individuals in the highest quartile of the wGRS had a nearly three-fold increased risk of developing T2DM compared with the lowest quartile (AOR = 3.06, 95% CI = 1.92–4.88, p < 0.001). Similarly, the individuals with 17 or more risk alleles among the 19 loci tested were more likely to have T2DM than those with 0–12 risk alleles among the loci tested (AOR = 1.83, 95% CI = 1.13–2.96, p = 0.010, Figure 1).


Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese
Odds ratio (OR) of T2DM according to the wGRS (a) and cGRS (b).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036696&req=5

ijerph-13-00863-f001: Odds ratio (OR) of T2DM according to the wGRS (a) and cGRS (b).
Mentions: To investigate the cumulative effect of the risk alleles on T2DM risk, wGRS and cGRS were calculated for all participants. Four variants inSLC16A11, three in CDKAL1, two in C2CD4A/B, and two in IGF2BP2 were in strong linkage disequilibrium (r2 range from 0.78 to 1.00, Figure S1); therefore four variants in each gene with the highest OR in association analysis together with another 15 variants in 15 genes were used to construct genetic risk scores. The median wGRS was 0.98 (interquartile range (IQR): 0.71) and 0.83 (IQR: 0.46) in T2DM and controls, respectively, while the median cGRS was 15 (IQR: 4) and 14 (IQR: 4) in T2DM and controls, respectively. Both wGRS and cGRS were significantly associated with T2DM susceptibility (AOR = 1.93, 95% CI = 1.42–2.62, p < 0.001; AOR = 1.07, 95% CI = 1.01–1.13, p = 0.030, respectively). In addition, the individuals in the highest quartile of the wGRS had a nearly three-fold increased risk of developing T2DM compared with the lowest quartile (AOR = 3.06, 95% CI = 1.92–4.88, p < 0.001). Similarly, the individuals with 17 or more risk alleles among the 19 loci tested were more likely to have T2DM than those with 0–12 risk alleles among the loci tested (AOR = 1.83, 95% CI = 1.13–2.96, p = 0.010, Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the &ldquo;A&rdquo; allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p &lt; 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92&ndash;4.88, p &lt; 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility.

No MeSH data available.