Fig. 4: Functional networks of ageing-related proteins and their longitudinal associations with clinical traits.

a, Four functional networks of ageing-related proteins identified by IPA. Red and blue dots represent gene names for proteins (Supplementary Table 2) that were positively and negatively associated with age (FDR < 0.5), respectively. b, Top five enriched GO terms or pathways based on Q values for ageing-related proteins from each of the four functional networks. All enriched GO terms and pathways are listed in Supplementary Table 7. c, Heatmap showing the longitudinal associations between 86 ageing-related proteins and 32 clinical traits in the GNHS discovery cohort (1,939 participants with 4,637 observations during follow-up), analysed by using linear mixed model adjusted for age, sex, measurement batch and instrument. Only significant associations are indicated (FDR < 0.05). The colour scale indicated the degree and direction of the associations. On the right side, the bar plot indicates the number of significant associations that were validated in the GNHS validation cohort (FDR < 0.05), and the line chart indicates the Pearson correlation for the associations between GNHS discovery and validation cohorts. BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides; TC, total cholesterol; FBG, fasting blood glucose; HbA1c, haemoglobin A1c; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF, tumour necrosis factor; ALT, alanine transaminase; AST, aspartate aminotransferase; SOD, superoxide dismutase; ALP, alkaline phosphatase; UA, urine acid; uCRE, urine creatinine; MMSE, Mini-Mental State Examination; MMSE1, immediate orientation; MMSE2, spatial orientation; MMSE3, temporal memory; MMSE4, attention; MMSE5, delayed recall, MMSE6, naming; MMSE7, verbal repetition; MMSE8, reading; MMSE9, verbal comprehension; MMSE10, writing; MMSE11, constructional praxis. Detailed results are presented in Supplementary Tables 8 and 9.