Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of “missing heritability” of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin model...

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Autores principales:	Yujia Ma, Zechen Zhou, Xiaoyi Li, Zeyu Yan, Kexin Ding, Dafang Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	type 2 diabetes indirect genetic effects heritability behavior-related phenotypes Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3430ba4ea1cf42b6a1e7e4b5c7a4f80b
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spelling	oai:doaj.org-article:3430ba4ea1cf42b6a1e7e4b5c7a4f80b2021-11-25T17:55:21ZExcess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus10.3390/ijms2222123181422-00671661-6596https://doaj.org/article/3430ba4ea1cf42b6a1e7e4b5c7a4f80b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12318https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of “missing heritability” of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of “missing heritability” of type 2 diabetes.Yujia MaZechen ZhouXiaoyi LiZeyu YanKexin DingDafang ChenMDPI AGarticletype 2 diabetesindirect genetic effectsheritabilitybehavior-related phenotypesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12318, p 12318 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes indirect genetic effects heritability behavior-related phenotypes Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	type 2 diabetes indirect genetic effects heritability behavior-related phenotypes Biology (General) QH301-705.5 Chemistry QD1-999 Yujia Ma Zechen Zhou Xiaoyi Li Zeyu Yan Kexin Ding Dafang Chen Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
description	We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of “missing heritability” of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of “missing heritability” of type 2 diabetes.
format	article
author	Yujia Ma Zechen Zhou Xiaoyi Li Zeyu Yan Kexin Ding Dafang Chen
author_facet	Yujia Ma Zechen Zhou Xiaoyi Li Zeyu Yan Kexin Ding Dafang Chen
author_sort	Yujia Ma
title	Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
title_short	Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
title_full	Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
title_fullStr	Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
title_full_unstemmed	Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus
title_sort	excess heritability contribution of alcohol consumption variants in the “missing heritability” of type 2 diabetes mellitus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3430ba4ea1cf42b6a1e7e4b5c7a4f80b
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Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus

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