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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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Author(s)
Sehoon ParkSoojin LeeYaerim KimYeonhee LeeMin Woo KangKwangsoo KimYong Chul KimSeung Seok HanHajeong LeeJung Pyo LeeKwon Wook JooChun Soo LimYon Su KimDong Ki Kim
Keimyung Author(s)
Kim, Yae Rim
Department
Dept. of Internal Medicine (내과학)
Journal Title
PLoS One
Issued Date
2021
Volume
16
Issue
7
Keyword
KidneysGeneticsGenome-wide association studiesCreatinineSingle nucleotide polymorphismsBody mass indexObesityGlomerular filtration rate
Abstract
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.
Keimyung Author(s)(Kor)
김예림
Publisher
School of Medicine (의과대학)
Citation
Sehoon Park et al. (2021). Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study. PLoS One, 16(7), e0254649. doi: 10.1371/journal.pone.0254649
Type
Article
ISSN
1932-6203
Source
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254649
DOI
10.1371/journal.pone.0254649
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43977
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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