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PLoS One. 2021;16(7):e0254649.

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

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제1저자 박세훈 · 교신저자 김동기

소속 (9)
  1. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
  2. Department of Internal Medicine, Armed Forces Capital Hospital, Gyeonggi-do, Korea.
  3. Division of Nephrology, Department of Internal Medicine, Uijeongbu Eulji University Medical Center, Gyeonggi-do, Korea.
  4. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
  5. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  6. Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea.
  7. Kidney Research Institute, Seoul National University, Seoul, Korea.
  8. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
  9. Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, Korea.

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.

Figures

Fig 1
Fig 1 Study flow diagram. CKD = chronic kidney disease, eGFR = estimated glomerular filtration rate, GWAS = genome-wide association study, SNP = single-nucleotide polymorphism, QC = quality control, MR = Mendelian randomization.
Fig 2
Fig 2 Generalized additive model demonstrating the association between eGFR and height adjusted for age and body mass index for each sex. The x-axes indicate the measured baseline height (cm), and the y-axes indicate zero-centered predictive values for eGFR based on generalized additive models. The broken lines indicate 95% confidence intervals. eGFR = estimated glomerular filtration rate.
Fig 3
Fig 3 Causal estimates of adult height on kidney function traits in the CKDGen GWAS meta-analysis (N = 567,460) and UK Biobank GWAS (N = 321,405). Kidney function parameters (eGFR and CKD) were based on serum creatinine values in the CKDGen GWAS meta-analysis and on serum cystatin C levels in the UK Biobank GWAS. eGFR was log-scaled in CKDGen data, and raw continuous values were used for UK Biobank data. Multivariable MR was performed with adjustment of the genetic effects of genetic instruments for body mass index. GWAS = genome-wide association study, eGFR = estimated glomerular filtration rate, CKD = chronic kidney disease. MR = Mendelian randomization, MR-IVW = Multiplicative random effect inverse variance weighting, MR-RAPS = Mendelian randomization-robust adjusted profile score, OR = odds ratio, CI = confidence interval.

그림 출처: PubMed Central 공개 논문 (PMC8321232)

Conflict of interest statement

The authors have declared that no competing interests exist.

그 밖의 정보
출판 형태
Journal Article, Observational Study
저널
PloS one · eISSN 1932-6203
전자 출판
2021-07-29
MeSH
Humans · Mendelian Randomization Analysis* · Middle Aged · Male · Female · Adult · Glomerular Filtration Rate* · Body Height* / genetics · Aged · Creatinine* / blood · Cross-Sectional Studies · Cystatin C / blood / genetics · Genome-Wide Association Study · Kidney / physiopathology · United Kingdom / epidemiology
Substances
Creatinine · Cystatin C
연구비
Medical Research Council MC_PC_17228 · Medical Research Council MC_QA137853
참고문헌
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