Environment-wide association study (EWAS) to identify factors associated with hematocrit: evidence from the Guangzhou Biobank Cohort Study

Purpose: In randomized controlled trials reducing high hematocrit (Hct) in patients with polycythemia vera protects against CVD events, whilst increasing Hct in anemia patients causes CVD events. Hct is influenced by environmental and life style factors. Given the limited knowledge concerning the drivers of Hct, we took an approach to identifying drivers of Hct.

Methods: We used an environment-wide association study (EWAS) to identify environmental and life style factors associated with Hct in 20443 older Chinese adults (mean age=62.7 years) from the Guangzhou Biobank Cohort Study. We evaluated the role of 25 nutrients, 40 environmental contaminants, 2 metals (only available for 10405 participants) and 6 life-style factors in relation to Hct, adjusted for sex, age, recruitment phase and social-economic position.

Results: In a mutually adjusted model vitamin A, serum calcium, serum magnesium and alcohol use were associated with higher Hct while physical activity was associated with lower Hct.

Conclusion: Despite the difficulty of ascertaining causality, finding both expected (vitamin A and physical inactivity) and novel factors (serum calcium, serum magnesium and alcohol use) strongly associated with Hct illustrates the utility of EWAS to generate hypotheses regarding the potential contribution of modifiable exposures to CVD.