Toward capturing the exposome variability: Household co-exposure patterns in the LIFE study Jake Chung Jan 2016

Questions Is it possible to characterize the density of correlations of environmental exposures? How are the correlations of exposures driven by shared environment (e.g., within household) vs. the individual? Aims 1. Explore the co-exposure patterns of chemical biomarkers from 12 classes 2. Examine the influence of familial relatedness in correlation of exposures Main findings Comparing females and males: 1. Highly similar co-exposure patterns between the male and female groups 2. Higher within-class Spearman correlations (abs. median r: 0.25 - 0.5) for persistent organic chemicals (PCBs, PBDEs, organochlorine pesticides) than other classes (<0.25) Comparing couples to above: 1. Both the abs median correlation (abs. median r: < 0.25) and interquartile ranges of correlation (32 to 80% reduction) of all chemical classes are lower

Method 1. Load imputed chemical data in R (provided by NICHD) 2. Obtain residuals from regressing chemicals against serum lipids and creatinine Linear model: scale(log10(biomarker+1)) ~ scale(creatinine) + scale(total lipids) Total lipid calculated by Philips’ formula 3. Get final Spearman correlation estimates by averaging 10 imputed frame (Rubin’s method)

Two generally positively correlated clusters: 1) PCBs, PFCs, organochlorine pesticides, and blood metals 2) phytoestrogens, phthalates, phenols, urinary metals and metalloids, and parabens Left: females; Right: males Interactive plots: https://www.ocf.berkeley.edu/~mkchung/corr/

Similar co-exposure patterns between females and males (red line represents perfect agreement)

Similar density curves between females and males

Weaker co-exposure pattern in couples! Females Males Interactive plots: https://www.ocf.berkeley.edu/~mkchung/corr/

Persistent organic chemicals have higher within-class correlations Left: females; Right: males

Lower within-class correlations in couples Females Males

Interpretation Co-exposure patterns of biomarkers were found in: Both between and within chemical classes With stronger within-class correlation for persistent organic chemicals (PCBs, PBDEs, OCPs) Implication: Analytical challenges for exposome-wide association study p value correction multicollinearity

2) Damping of correlations in couple group Chemical correlations were weaker in the couples than females and males Suggests People spend over 90% of their time indoor and more than 12 hours a day at home Couple shares home environment but with weak co-exposure patterns Non-home environment could be a significant source of exposure variability Implication Surrogates such as house dust are commonly used to assess exposures For life-course, family-based (e.g. fecundity, twin studies), taking only household indoor surrogates for exposure assessment may cause a bias in epidemiological findings. Could be especially of a concern to persistent organic chemicals with endocrine disrupting capability that shown higher reduction in correlations