Associations of 2923 Olink proteins with demographic, lifestyle, environmental and health characteristics in middle-aged Chinese adults

Previous studies have identified a large number of genetic variants affecting plasma levels of proteins, but little is known about the non-genetic factors influencing plasma levels of proteins in diverse populations. We measured plasma levels of 2923 proteins, using Olink Explore platform, in 2006 participants (mean age = 50.8 years; 62% female; mean body mass index = 23.9 kg/m2) in the China Kadoorie Biobank, without prior cardiovascular diseases. Linear regression analyses were used to assess the associations of individual proteins with 37 major 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 findings in UK Biobank. Overall 31 exposures were associated with at least one protein, with age (n = 1154), sex (n = 827), body mass index (n = 869) showing the highest number of associations, followed by frailty index (n = 597), systolic blood pressure (n = 479), random plasma glucose (n = 387), ambient temperature (n = 292), and hepatitis B surface antigen positivity (n = 282), but with diet and physical activity showing little associations. Likewise, of the 2,923 proteins examined, 65% were associated with at least one exposure, with 25 proteins associated with ≥ 10 exposures, including five (CDH2, ADGRE2, ADGRD1, ACY1, MEGF9) after mutual adjustments. The patterns of associations were similar after further mutual adjustments for exposures examined but differed by sex, chiefly due to differences in lifestyle and reproductive factors. Most of the observed associations were replicated in the Europeans.