Exposome-wide association studies require larger sample sizes to discover unbiased associations between semen quality and endocrine disruptor exposures
- Ming Kei (Jake) Chung
- Germaine M. Buck Louis
- email: glouis[at]gmu[dot]edu
- Kurunthachalam Kannan
- email: kurunthachalam[dot]kannan[at]health[dot]ny[dot]gov
- Chirag J. Patel
- github: @chiragjp
- web: www.chiragjpgroup.org
Exposome-wide association studies (EWAS) are a way to prioritize multiple environmental factors associated with phenotypic traits in large sample sizes. However, its utility for smaller reproductive cohort studies is unknown and served as the impetus for study.
We conducted 1) a multivariate EWAS of 128 endocrine disrupting chemicals (EDCs) from 15 chemical classes measured in urine/serum relative to 7 semen quality endpoints in a prospective cohort study comprising 473 men and 2) estimated the sample size requirements for EWAS etiologic investigations.
None of the EDCs was associated with semen quality endpoints after adjusting for multiple tests. However, several EDCs (e.g., polychlorinated biphenyl congeners 99, 105, 114, and 167) were associated with raw p ≤ 0.05. In a post hoc statistical power analysis using the observed effect sizes, we determined that EWAS research will require a mean sample size of 2696 men (1795 – 3625) to attain a power of 0.8. The average size of four published studies is 201 men.
Cohort studies with hundreds of participants are underpowered (< 0.8) for EWAS-related investigations. Merging cohorts to ensure a sufficient sample size can facilitate the use of EWAS methods for assessing EDC mixtures and delineating those that impact semen quality.
- This github repository hosts analytical materials for estimating sample size requirement for EWAS, using LIFE Study data.
- Code for data clean-up, processing, analysis, and visulization can be found on GitHub
- Main findings of our study can be found here
- Please contact us for further information, thank you.