Separating the effects of childhood and adult body size on inflammatory arthritis: a Mendelian randomisation study

Objectives Using Mendelian randomisation (MR), we examined whether childhood body size affects risk of rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), gout and systemic lupus erythematosus (SLE) after accounting for the effect of adult body size. Methods Genetic instruments for childhood (age 10 years) and adult body size were derived using data from 453 169 individuals from the UK Biobank study (313 and 580 variants respectively), which have been previously validated using body mass index data from three independent populations. Genome-wide association data comprised 22 350 RA, 9069 AS, 3609 PsA, 13 179 gout and 5201 SLE cases. For each outcome, we conducted univariable MR to estimate the total effects of childhood and adult body size, and multivariable MR to examine the independent effect of childhood body size after accounting for adult body size. Results Genetically predicted childhood body size had a total effect on risk of PsA (OR 2.18 per change in body size category; 95% CI 1.43 to 3.31), gout (OR 2.18; 95% CI 1.43 to 3.31) and SLE (OR 2.44; 95% CI 1.14 to 5.22), but not RA (OR 0.95; 95% CI 0.70 to 1.29) or AS (OR 0.96; 95% CI 0.61 to 1.52). After accounting for adult body size, the direct effect of childhood body size was little changed for PsA (OR 1.92; 1.14 to 3.25) and SLE (OR 2.69; 1.24 to 5.87) but was attenuated for gout (OR 1.40; 95% CI 0.94 to 2.09). Conclusions Our findings suggest that, for PsA and SLE, the risk conferred from having a larger body size during childhood may not be fully reversable even when a healthy size is achieved in adulthood.