Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.

As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association...

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Autores principales:	Sehoon Park, Soojin Lee, Yaerim Kim, Yeonhee Lee, Min Woo Kang, Kwangsoo Kim, Yong Chul Kim, Seung Seok Han, Hajeong Lee, Jung Pyo Lee, Kwon Wook Joo, Chun Soo Lim, Yon Su Kim, Dong Ki Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/047f1342cd204755b42e68cf292be110
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spelling	oai:doaj.org-article:047f1342cd204755b42e68cf292be1102021-12-02T20:08:57ZCausal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.1932-620310.1371/journal.pone.0254649https://doaj.org/article/047f1342cd204755b42e68cf292be1102021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254649https://doaj.org/toc/1932-6203As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40-69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.Sehoon ParkSoojin LeeYaerim KimYeonhee LeeMin Woo KangKwangsoo KimYong Chul KimSeung Seok HanHajeong LeeJung Pyo LeeKwon Wook JooChun Soo LimYon Su KimDong Ki KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254649 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sehoon Park Soojin Lee Yaerim Kim Yeonhee Lee Min Woo Kang Kwangsoo Kim Yong Chul Kim Seung Seok Han Hajeong Lee Jung Pyo Lee Kwon Wook Joo Chun Soo Lim Yon Su Kim Dong Ki Kim Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
description	As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40-69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.
format	article
author	Sehoon Park Soojin Lee Yaerim Kim Yeonhee Lee Min Woo Kang Kwangsoo Kim Yong Chul Kim Seung Seok Han Hajeong Lee Jung Pyo Lee Kwon Wook Joo Chun Soo Lim Yon Su Kim Dong Ki Kim
author_facet	Sehoon Park Soojin Lee Yaerim Kim Yeonhee Lee Min Woo Kang Kwangsoo Kim Yong Chul Kim Seung Seok Han Hajeong Lee Jung Pyo Lee Kwon Wook Joo Chun Soo Lim Yon Su Kim Dong Ki Kim
author_sort	Sehoon Park
title	Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
title_short	Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
title_full	Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
title_fullStr	Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
title_full_unstemmed	Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.
title_sort	causal linkage between adult height and kidney function: an integrated population-scale observational analysis and mendelian randomization study.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/047f1342cd204755b42e68cf292be110
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Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study.

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