Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population
BackgroundUntil recently, genome-wide association study (GWAS)-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM) or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration...
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2014-10-01
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| Series: | Diabetes & Metabolism Journal |
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| Online Access: | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-38-375.pdf |
| _version_ | 1818020621178634240 |
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| author | Min Jin Go Joo-Yeon Hwang Tae-Joon Park Young Jin Kim Ji Hee Oh Yeon-Jung Kim Bok-Ghee Han Bong-Jo Kim |
| author_facet | Min Jin Go Joo-Yeon Hwang Tae-Joon Park Young Jin Kim Ji Hee Oh Yeon-Jung Kim Bok-Ghee Han Bong-Jo Kim |
| author_sort | Min Jin Go |
| collection | DOAJ |
| description | BackgroundUntil recently, genome-wide association study (GWAS)-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM) or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population.MethodsWe performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842). The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500). A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively.ResultsA combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356) loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of β-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study.ConclusionOur study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population. |
| first_indexed | 2024-04-14T08:07:40Z |
| format | Article |
| id | doaj.art-fa6a27a479984a5a95ef22b8574f49af |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-04-14T08:07:40Z |
| publishDate | 2014-10-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-fa6a27a479984a5a95ef22b8574f49af2022-12-22T02:04:41ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872014-10-0138537538710.4093/dmj.2014.38.5.37514646Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean PopulationMin Jin GoJoo-Yeon HwangTae-Joon ParkYoung Jin KimJi Hee OhYeon-Jung KimBok-Ghee HanBong-Jo KimBackgroundUntil recently, genome-wide association study (GWAS)-based findings have provided a substantial genetic contribution to type 2 diabetes mellitus (T2DM) or related glycemic traits. However, identification of allelic heterogeneity and population-specific genetic variants under consideration of potential confounding factors will be very valuable for clinical applicability. To identify novel susceptibility loci for T2DM and glycemic traits, we performed a two-stage genetic association study in a Korean population.MethodsWe performed a logistic analysis for T2DM, and the first discovery GWAS was analyzed for 1,042 cases and 2,943 controls recruited from a population-based cohort (KARE, n=8,842). The second stage, de novo replication analysis, was performed in 1,216 cases and 1,352 controls selected from an independent population-based cohort (Health 2, n=8,500). A multiple linear regression analysis for glycemic traits was further performed in a total of 14,232 nondiabetic individuals consisting of 7,696 GWAS and 6,536 replication study participants. A meta-analysis was performed on the combined results using effect size and standard errors estimated for stage 1 and 2, respectively.ResultsA combined meta-analysis for T2DM identified two new (rs11065756 and rs2074356) loci reaching genome-wide significance in CCDC63 and C12orf51 on the 12q24 region. In addition, these variants were significantly associated with fasting plasma glucose and homeostasis model assessment of β-cell function. Interestingly, two independent single nucleotide polymorphisms were associated with sex-specific stratification in this study.ConclusionOur study showed a strong association between T2DM and glycemic traits. We further observed that two novel loci with multiple diverse effects were highly specific to males. Taken together, these findings may provide additional insights into the clinical assessment or subclassification of disease risk in a Korean population.http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-38-375.pdfGenome-wide association studyGlycemic traitSex-specificType 2 diabetes |
| spellingShingle | Min Jin Go Joo-Yeon Hwang Tae-Joon Park Young Jin Kim Ji Hee Oh Yeon-Jung Kim Bok-Ghee Han Bong-Jo Kim Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population Diabetes & Metabolism Journal Genome-wide association study Glycemic trait Sex-specific Type 2 diabetes |
| title | Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population |
| title_full | Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population |
| title_fullStr | Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population |
| title_full_unstemmed | Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population |
| title_short | Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population |
| title_sort | genome wide association study identifies two novel loci with sex specific effects for type 2 diabetes mellitus and glycemic traits in a korean population |
| topic | Genome-wide association study Glycemic trait Sex-specific Type 2 diabetes |
| url | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-38-375.pdf |
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