Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function

BackgroundObservational studies have shown possible bidirectional association between type 2 diabetes (T2D) and pulmonary function, but the causality is not well defined. The purpose of this study is to investigate genetic correlation and causal relationship of T2D and glycemic traits with pulmonary...

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Autores principales:	Jiahao Zhu, Huanling Zhao, Dingwan Chen, Lap Ah Tse, Sanjay Kinra, Yingjun Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glycemic traits linkage disequilibrium score regression pulmonary function Mendelian randomization type 2 diabetes Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/2bf515a90d52425d9735eed783d10d6c
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spelling	oai:doaj.org-article:2bf515a90d52425d9735eed783d10d6c2021-12-01T01:10:47ZGenetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function1664-239210.3389/fendo.2021.777487https://doaj.org/article/2bf515a90d52425d9735eed783d10d6c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.777487/fullhttps://doaj.org/toc/1664-2392BackgroundObservational studies have shown possible bidirectional association between type 2 diabetes (T2D) and pulmonary function, but the causality is not well defined. The purpose of this study is to investigate genetic correlation and causal relationship of T2D and glycemic traits with pulmonary function.MethodsBy leveraging summary statistics from large-scale genome-wide association studies, linkage disequilibrium score regression was first implemented to quantify genetic correlations between T2D, glycemic traits, and several spirometry indices. Then both univariable and multivariable Mendelian randomization analyses along with multiple pleiotropy-robust methods were performed in two directions to assess the causal nature of these relationships.ResultsForced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) showed significant genetic correlations with T2D and fasting insulin levels and suggestive genetic correlations with fasting glucose and hemoglobin A1c. In Mendelian randomization analyses, genetically predicted higher FEV1 (OR = 0.77; 95% CI = 0.63, 0.94) and FVC (OR = 0.82; 95% CI = 0.68, 0.99) were significantly associated with lower risk of T2D. Conversely, genetic predisposition to higher risk of T2D exhibited strong association with reduced FEV1 (beta = −0.062; 95% CI = −0.100, −0.024) and FEV1 (beta = −0.088; 95% CI = −0.126, −0.050) and increased FEV1/FVC ratio (beta = 0.045; 95% CI = 0.012, 0.078). We also found a suggestive causal effect of fasting glucose on pulmonary function and of pulmonary function on fasting insulin and proinsulin.ConclusionsThe present study provided supportive evidence for genetic correlation and bidirectional causal association between T2D and pulmonary function. Further studies are warranted to clarify possible mechanisms related to lung dysfunction and T2D, thus offering a new strategy for the management of the two comorbid diseases.Jiahao ZhuHuanling ZhaoDingwan ChenLap Ah TseSanjay KinraYingjun LiFrontiers Media S.A.articleglycemic traitslinkage disequilibrium score regressionpulmonary functionMendelian randomizationtype 2 diabetesDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glycemic traits linkage disequilibrium score regression pulmonary function Mendelian randomization type 2 diabetes Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	glycemic traits linkage disequilibrium score regression pulmonary function Mendelian randomization type 2 diabetes Diseases of the endocrine glands. Clinical endocrinology RC648-665 Jiahao Zhu Huanling Zhao Dingwan Chen Lap Ah Tse Sanjay Kinra Yingjun Li Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
description	BackgroundObservational studies have shown possible bidirectional association between type 2 diabetes (T2D) and pulmonary function, but the causality is not well defined. The purpose of this study is to investigate genetic correlation and causal relationship of T2D and glycemic traits with pulmonary function.MethodsBy leveraging summary statistics from large-scale genome-wide association studies, linkage disequilibrium score regression was first implemented to quantify genetic correlations between T2D, glycemic traits, and several spirometry indices. Then both univariable and multivariable Mendelian randomization analyses along with multiple pleiotropy-robust methods were performed in two directions to assess the causal nature of these relationships.ResultsForced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) showed significant genetic correlations with T2D and fasting insulin levels and suggestive genetic correlations with fasting glucose and hemoglobin A1c. In Mendelian randomization analyses, genetically predicted higher FEV1 (OR = 0.77; 95% CI = 0.63, 0.94) and FVC (OR = 0.82; 95% CI = 0.68, 0.99) were significantly associated with lower risk of T2D. Conversely, genetic predisposition to higher risk of T2D exhibited strong association with reduced FEV1 (beta = −0.062; 95% CI = −0.100, −0.024) and FEV1 (beta = −0.088; 95% CI = −0.126, −0.050) and increased FEV1/FVC ratio (beta = 0.045; 95% CI = 0.012, 0.078). We also found a suggestive causal effect of fasting glucose on pulmonary function and of pulmonary function on fasting insulin and proinsulin.ConclusionsThe present study provided supportive evidence for genetic correlation and bidirectional causal association between T2D and pulmonary function. Further studies are warranted to clarify possible mechanisms related to lung dysfunction and T2D, thus offering a new strategy for the management of the two comorbid diseases.
format	article
author	Jiahao Zhu Huanling Zhao Dingwan Chen Lap Ah Tse Sanjay Kinra Yingjun Li
author_facet	Jiahao Zhu Huanling Zhao Dingwan Chen Lap Ah Tse Sanjay Kinra Yingjun Li
author_sort	Jiahao Zhu
title	Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
title_short	Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
title_full	Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
title_fullStr	Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
title_full_unstemmed	Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function
title_sort	genetic correlation and bidirectional causal association between type 2 diabetes and pulmonary function
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2bf515a90d52425d9735eed783d10d6c
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_version_	1718406013113073664

Genetic Correlation and Bidirectional Causal Association Between Type 2 Diabetes and Pulmonary Function

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