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Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population
BACKGROUND: Until 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 consideratio...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Diabetes Association
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209352/ https://www.ncbi.nlm.nih.gov/pubmed/25349825 http://dx.doi.org/10.4093/dmj.2014.38.5.375 |
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author | Go, Min Jin Hwang, Joo-Yeon Park, Tae-Joon Kim, Young Jin Oh, Ji Hee Kim, Yeon-Jung Han, Bok-Ghee Kim, Bong-Jo |
author_facet | Go, Min Jin Hwang, Joo-Yeon Park, Tae-Joon Kim, Young Jin Oh, Ji Hee Kim, Yeon-Jung Han, Bok-Ghee Kim, Bong-Jo |
author_sort | Go, Min Jin |
collection | PubMed |
description | BACKGROUND: Until 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. METHODS: We 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. RESULTS: A 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. CONCLUSION: Our 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. |
format | Online Article Text |
id | pubmed-4209352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Korean Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-42093522014-10-27 Genome-Wide Association Study Identifies Two Novel Loci with Sex-Specific Effects for Type 2 Diabetes Mellitus and Glycemic Traits in a Korean Population Go, Min Jin Hwang, Joo-Yeon Park, Tae-Joon Kim, Young Jin Oh, Ji Hee Kim, Yeon-Jung Han, Bok-Ghee Kim, Bong-Jo Diabetes Metab J Original Article BACKGROUND: Until 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. METHODS: We 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. RESULTS: A 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. CONCLUSION: Our 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. Korean Diabetes Association 2014-10 2014-10-17 /pmc/articles/PMC4209352/ /pubmed/25349825 http://dx.doi.org/10.4093/dmj.2014.38.5.375 Text en Copyright © 2014 Korean Diabetes Association http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Go, Min Jin Hwang, Joo-Yeon Park, Tae-Joon Kim, Young Jin Oh, Ji Hee Kim, Yeon-Jung Han, Bok-Ghee Kim, Bong-Jo 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 | 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 | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209352/ https://www.ncbi.nlm.nih.gov/pubmed/25349825 http://dx.doi.org/10.4093/dmj.2014.38.5.375 |
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