Toward Capturing the Exposome: Exposure Biomarker Variability and Coexposure Patterns in the Shared Environment

Abstract

Many factors affect the variation in the exposome. We examined the influence of shared household and partner's sex in relation to the variation in 128 endocrine disrupting chemical (EDC) exposures among couples. In a cohort comprising of 501 couples trying for pregnancy, we measured 128 (13 chemical classes) persistent and nonpersistent EDCs and estimated 1) sex-specific differences; 2) variance explained by shared household; and 3) Spearman's rank correlation coefficients ( r_s) for females, males, and couples' exposures. Sex was correlated with 8 EDCs including per- and polyfluoroalkyl substances (PFASs) ( p < 0.05). Shared household explained 43% and 41% of the total variance for PFASs and blood metals, respectively, but less than 20% for the remaining 11 EDC classes. Coexposure patterns of the exposome were similar between females and males, with within-class r_s higher for persistent than for nonpersistent chemicals. Median r_ss of polybrominated compounds and urine metalloids were 0.45 and 0.09, respectively, for females (0.41 and 0.08 for males; 0.21 and 0.04 for couples). Our findings suggest that individual, rather than shared environment, could be a major factor influencing the covariation of the exposome. Understanding the correlations of exposures has important analytical and sampling implications for exposomics research.

Figure 1

Analytical scheme to investigate the exposures’ variability and correlations. A) We first extract the residuals from a linear model after adjusting for the base covariates (total lipids or creatinine) to calculate the Spearman’s rank correlation (r_s). B) Then, we used another linear model with an additional age variable to obtain residuals and conducted a paired t test to test the difference of chemicals between female and male partners in the same household. C) Afterward, we further adjusted for sex prior to extracting residuals to calculate the percentage of chemical variance explained by the shared environment.

Figure 2

Summary of the percentage of chemical variance explained by the shared (household) environment. Boxplots of the adjusted coefficient of determination (R²) within different chemical classes are shown. Interquartile range is not shown for the cotinine class because it contains only 1 compound. For each box, median and interquartile ranges are drawn, and the whiskers are extended to the largest values within 1.5*interquartile range. Black dots denote correlations outside of the range covered by the whiskers.

Figure 3

Exposome correlation globe showing the relationships of biomarkers between females, males, and couples. Right-half represents biomarkers in females; left-half represents biomarkers in males. Only Spearman’s rank correlations greater than 0.25 and smaller than −0.25 were shown as connections in the globe. Red line denotes positive correlation, and dark green line denotes a negative one. Color intensity and line width are proportional to the size of the correlation. Within-class and between-class correlations are shown outside and inside of the track respectively. Correlations in couples are indicated by the lines linking females and males (i.e., crossing the vertical-half of the globe).

Figure 4

Boxplots of Spearman’s rank correlations (r_s) within different chemical classes: A) females; B) males; and C) couples. For couples, summary statistics were estimated with the full 128 × 128 correlation matrix instead of with the half triangle. Certain classes contain only 1 pair of correlation (paracetamols in females, paracetamols in males, and cotinine in couples). “All” represents the grouping by the correlation of all pairs of chemicals available. The horizontal line drawn across the chemical classes is equal to the 95th percentile of the null distribution obtained from permuting the concentrations of all chemicals. For each box, median and interquartile ranges are drawn, and the whiskers are extended to the largest values within 1.5*interquartile range. Black dots denote correlations outside of the range covered by the whiskers.