Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis.
BACKGROUND: Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3988150?pdf=render |
| _version_ | 1817977610411442176 |
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| author | Yi-Cheng Chang Pi-Hua Liu Yu-Hsiang Yu Shan-Shan Kuo Tien-Jyun Chang Yi-Der Jiang Jiun-Yi Nong Juey-Jen Hwang Lee-Ming Chuang Lee-Ming Chuang |
| author_facet | Yi-Cheng Chang Pi-Hua Liu Yu-Hsiang Yu Shan-Shan Kuo Tien-Jyun Chang Yi-Der Jiang Jiun-Yi Nong Juey-Jen Hwang Lee-Ming Chuang Lee-Ming Chuang |
| author_sort | Yi-Cheng Chang |
| collection | DOAJ |
| description | BACKGROUND: Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated. METHODS: We analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese. RESULTS: Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations. CONCLUSION: We confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction. |
| first_indexed | 2024-04-13T22:18:40Z |
| format | Article |
| id | doaj.art-d0d16c746bfa45eca3b969db6cbf0eda |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T22:18:40Z |
| publishDate | 2014-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-d0d16c746bfa45eca3b969db6cbf0eda2022-12-22T02:27:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9504510.1371/journal.pone.0095045Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis.Yi-Cheng ChangPi-Hua LiuYu-Hsiang YuShan-Shan KuoTien-Jyun ChangYi-Der JiangJiun-Yi NongJuey-Jen HwangLee-Ming ChuangLee-Ming ChuangBACKGROUND: Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated. METHODS: We analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese. RESULTS: Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations. CONCLUSION: We confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.http://europepmc.org/articles/PMC3988150?pdf=render |
| spellingShingle | Yi-Cheng Chang Pi-Hua Liu Yu-Hsiang Yu Shan-Shan Kuo Tien-Jyun Chang Yi-Der Jiang Jiun-Yi Nong Juey-Jen Hwang Lee-Ming Chuang Lee-Ming Chuang Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. PLoS ONE |
| title | Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. |
| title_full | Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. |
| title_fullStr | Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. |
| title_full_unstemmed | Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. |
| title_short | Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis. |
| title_sort | validation of type 2 diabetes risk variants identified by genome wide association studies in han chinese population a replication study and meta analysis |
| url | http://europepmc.org/articles/PMC3988150?pdf=render |
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