An exposome-wide assessment of 6600 SomaScan proteins with non-genetic factors in Chinese adults

Background Proteomics offer new insights into human biology and disease aetiology. Previous studies have explored the associations of SomaScan proteins with multiple non-genetic factors, but they typically involved Europeans and a limited range of factors, with no evidence from East Asia populations. Methods We measured plasma levels of 6,597 unique human proteins using SomaScan platform in ∼2,000 participants in the China Kadoorie Biobank. Linear regression was used to examine the cross-sectional associations of 37 exposures across several different domains (e.g., socio-demographic, lifestyle, environmental, sample processing, reproductive factors, clinical measurements and frailty indices) with plasma concentrations of specific proteins, adjusting for potential confounders and multiple testing. Findings Overall 12 exposures were significantly associated with levels of >50 proteins, with sex (n=996), age (n=982), ambient temperature (n=802) and BMI (n=1035) showing the largest number of associations, followed by frailty indices (n=465) and clinical measurements (e.g., RPG, SBP), but not diet and physical activity which showed little associations. Many of these associations varied by sex, with a large number of age-related proteins in females also associated with menopausal status. Of the 6,597 proteins examined, 43% were associated with at least one exposure, with the proportion higher for high-abundance proteins, but certain biologically-important low-abundance proteins (e.g., PSA, HBD-4) were also associated with multiple exposures. The patterns of associations appeared generally similar to those with Olink proteins. Interpretation In Chinese adults an exposome-wide assessment of SomaScan proteins identified a large number of associations with exposures and health-related factors, informing future research and analytic strategies.