Separating the Effects of Early-Life and Adult Body Size on Chronic Kidney Disease Risk: A Mendelian Randomization...

Area of Science:

• Genetics
• Epidemiology
• Nephrology

Background:

• The causal link between childhood obesity and chronic kidney disease (CKD) risk is debated.
• Understanding the independent effects of body size in childhood versus adulthood on CKD is crucial.

Purpose of the Study:

• To investigate the independent contributions of early-life and adult body size to the risk of developing CKD.
• To utilize a Mendelian randomization (MR) approach to assess these relationships.

Main Methods:

• Employed univariate and multivariate Mendelian randomization (MR) analyses.
• Utilized genome-wide association study data from UK Biobank for body size in 453,169 participants.
• Incorporated CKD genetic association data from the CKDGen and FinnGen consortia.

Main Results:

• Genetically predicted larger early-life body size showed an initial association with increased CKD risk and blood urea nitrogen (BUN) levels.
• This association between early-life body size and CKD/BUN was not significant after adjusting for adult body size.
• Genetically predicted larger adult body size was significantly associated with increased CKD risk, decreased estimated glomerular filtration rate (eGFR), and increased BUN levels.

Conclusions:

• The observed link between early-life body size and CKD risk appears to be mediated by the persistence of larger body size into adulthood.
• Adult body size is a significant independent risk factor for CKD.