| Title: | Causal linkage between adult height and kidney function: An integrated population-scale observational analysis and Mendelian randomization study |
| Journal: | PLOS ONE |
| Published: | 29 Jul 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34324541/ |
| DOI: | https://doi.org/10.1371/journal.pone.0254649 |
| URL: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0254649&type=printable |
Publication 4453
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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.14 Authors
- 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
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