In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 7 ( 2021-7-29), p. e0254649-
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 (eGFR creatinine ) or cystatin C (eGFR cystatinC ) 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 eGFR creatinine and CKD creatinine 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 eGFR cystatinC and CKD cystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFR creatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P 〈 0.001) and eGFR cystatinC (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-eGFR creatinine (adjusted beta -0.007, standard error 0.001, P 〈 0.001) and a higher risk of CKD creatinine (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 eGFR cystatinC (adjusted beta -1.303, standard error 0.140, P 〈 0.001) and CKD cystatinC (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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0254649
DOI:
10.1371/journal.pone.0254649.g001
DOI:
10.1371/journal.pone.0254649.g002
DOI:
10.1371/journal.pone.0254649.g003
DOI:
10.1371/journal.pone.0254649.t001
DOI:
10.1371/journal.pone.0254649.t002
DOI:
10.1371/journal.pone.0254649.t003
DOI:
10.1371/journal.pone.0254649.s001
DOI:
10.1371/journal.pone.0254649.s002
DOI:
10.1371/journal.pone.0254649.s003
DOI:
10.1371/journal.pone.0254649.s004
DOI:
10.1371/journal.pone.0254649.s005
DOI:
10.1371/journal.pone.0254649.s006
DOI:
10.1371/journal.pone.0254649.s007
DOI:
10.1371/journal.pone.0254649.s008
DOI:
10.1371/journal.pone.0254649.s009
DOI:
10.1371/journal.pone.0254649.s010
DOI:
10.1371/journal.pone.0254649.s011
DOI:
10.1371/journal.pone.0254649.s012
DOI:
10.1371/journal.pone.0254649.s013
DOI:
10.1371/journal.pone.0254649.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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