Circulating insulin-like growth factor-I and risk of 25 common conditions: outcome-wide analyses in the UK Biobank Study

BackgroundWhile there is strong epidemiological evidence that circulating insulin-like growth factor-I (IGF-I) is associated with a higher risk of several cancers, little is known about its association with non-cancer outcomes. We investigated associations of circulating IGF-I with risk of 25 common conditions, other than cancer, in a large British cohort. MethodsStudy participants were 318 749 middle-aged adults enrolled in the UK Biobank Study. Serum IGF-I concentration was measured in samples collected at baseline (2006-2010), and re-measured in 12 334 participants after an average of 4.3 years. We followed-up participants over an average of 11.5 years by linking to hospital admissions and mortality registries. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between circulating IGF-I and 25 common conditions, using the repeated IGF-I measurements to correct for regression dilution bias. ResultsAfter correction for multiple testing (P<0.002), IGF-I was positively associated with carpal tunnel syndrome (HR per 5 nmol/l higher concentration=1.12, 95% CI, 1.08-1.16), and inversely associated with varicose veins (0.90, 0.85-0.95), cataracts (0.97, 0.95-0.99), diabetes (0.92, 0.90-0.95), and iron deficiency anaemia (0.90, 0.86-0.93). The associations for cataracts and diabetes attenuated when restricted to cases diagnosed after five or more years of follow-up, suggesting that these associations were likely affected by reverse causality. ConclusionsHigher IGF-I concentration might be associated with the risk for several conditions, but genetic studies are needed to clarify which associations may be causal. Key messagesO_LIEvidence on the association between circulating insulin-like growth factor-I (IGF-I) and risk of many common, non-cancer health outcomes in the general population is relatively limited. C_LIO_LIThis study used an outcome-wide approach to prospectively examine associations of circulating IGF-I with risk of 25 common conditions in a large, prospective cohort of over 300,000 UK adults. C_LIO_LIOur study showed that circulating IGF-I is associated with risks of several common diseases and conditions; IGF-I was positively associated with carpal tunnel syndrome and inversely associated with varicose veins, cataracts, diabetes, and iron deficiency anaemia. C_LIO_LIFurther research is needed to evaluate whether these differences in risk may reflect causal relationships. C_LI