An exposome-wide investigation of 2923 Olink proteins with non-genetic factors in Chinese adults

BackgroundPrevious studies in European populations have identified a large number of genetic variants affecting plasma levels of Olink proteins, but little is known about the non-genetic factors influencing plasma levels of proteins, particularly in Chinese populations. MethodsWe measured plasma levels of 2,923 proteins, using Olink Explore platform, in 2,006 participants in the China Kadoorie Biobank. Linear regression analyses were used to assess the cross-sectional associations of individual proteins with 37 exposures across multiple domains (e.g. socio-demographic, lifestyle, environmental, sample processing, reproductive factors, clinical measurements, and health-related indices), adjusted for potential confounders and multiple testing. These were further replicated and compared with similar analyses in Europeans. ResultsOverall 31 exposures were associated with at least one protein, with age (n=1,154), sex (n=827), BMI (n=869) showing the highest number of associations, followed by frailty index (n=597), SBP (n=479), RPG (n=387), ambient temperature (n=292), and HBsAg-positivity (n=282), with diet and physical activity showing little associations. Likewise, of the 2,923 proteins examined, 65% were associated with at least one exposure, with three proteins (CDHR2, CKB, and PLAT) showing the largest number of associations with baseline characteristics (n=14). The patterns of associations differed by sex, chiefly due to differences in lifestyle and reproductive factors. Over 90% of proteomic associations with key exposures in the current study were replicated in the UK Biobank. ConclusionsIn Chinese adults, the exposome-wide assessment of Olink proteins identified a large number of associations with a wide range of exposures, which could inform future research priorities and analytic strategies.