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Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians

Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a sign...

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Autores principales: Choi, Ji-Young, Jang, Hye-Mi, Han, Sohee, Hwang, Mi Yeong, Kim, Bong-Jo, Kim, Young Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korea Genome Organization 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944053/
https://www.ncbi.nlm.nih.gov/pubmed/31896248
http://dx.doi.org/10.5808/GI.2019.17.4.e48
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author Choi, Ji-Young
Jang, Hye-Mi
Han, Sohee
Hwang, Mi Yeong
Kim, Bong-Jo
Kim, Young Jin
author_facet Choi, Ji-Young
Jang, Hye-Mi
Han, Sohee
Hwang, Mi Yeong
Kim, Bong-Jo
Kim, Young Jin
author_sort Choi, Ji-Young
collection PubMed
description Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner’s curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33–0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.
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spelling pubmed-69440532020-01-09 Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians Choi, Ji-Young Jang, Hye-Mi Han, Sohee Hwang, Mi Yeong Kim, Bong-Jo Kim, Young Jin Genomics Inform Original Article Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner’s curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33–0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis. Korea Genome Organization 2019-12-20 /pmc/articles/PMC6944053/ /pubmed/31896248 http://dx.doi.org/10.5808/GI.2019.17.4.e48 Text en (c) 2019, Korea Genome Organization (CC) This is an open-access article distributed under the terms of the Creative Commons Attribution license(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Choi, Ji-Young
Jang, Hye-Mi
Han, Sohee
Hwang, Mi Yeong
Kim, Bong-Jo
Kim, Young Jin
Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title_full Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title_fullStr Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title_full_unstemmed Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title_short Recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126K East Asians
title_sort recapitulation of previously reported associations for type 2 diabetes and metabolic traits in the 126k east asians
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944053/
https://www.ncbi.nlm.nih.gov/pubmed/31896248
http://dx.doi.org/10.5808/GI.2019.17.4.e48
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