Lifestyle differences between co-twins are associated with decreased similarity in their internal and external exposome profiles

Whether differences in lifestyle between co-twins are reflected in differences in their internal or external exposome profiles remains largely underexplored. We therefore investigated whether within-pair differences in lifestyle were associated with within-pair differences in exposome profiles across four domains: the external exposome, proteome, metabolome and epigenetic age acceleration (EAA). For each domain, we assessed the similarity of co-twin profiles using Gaussian similarities in up to 257 young adult same-sex twin pairs (54% monozygotic). We additionally tested whether similarity in one domain translated into greater similarity in another. Results suggest that a lower degree of similarity in co-twins' exposome profiles was associated with greater differences in their behavior and substance use. The strongest association was identified between excessive drinking behavior and the external exposome. Overall, our study demonstrates how social behavior and especially substance use are connected to the internal and external exposomes, while controlling for familial confounders.


Section 1
We investigated the e ect of exposome WPPS skewness on the results obtained in analyses involving this domain.Sensitivity analysis 1 consisted in taking the logit of the WPPS of the external exposome to reduce skewness of this variable.Sensitivity analysis 2 consisted in excluding individuals with a WPPS of 1 from the analyses.

Sensitivity analysis 1:
The skewness was reduced from -0.73 to -0.31 by using the logit of the WPPS.Pairwise associations between WPPS showed that the association between proteome and external exposome remained positive and signi cant in all pairs (p=0.04) and MZ pairs (p=0.05),but not DZ pairs (p=0.88).The other associations were not signi cant.This was consistent with the results of the main analyses.

Sensitivity analysis 2:
In twin pairs in which the WPPS of the external exposome was not 1 (N pairs=170), the pairwise association between the WPPS of the proteome and that of the external exposome was no longer signi cant in all pairs (estimate: 0.22; standard error: 0.18; p=0.23) and in MZ pairs (estimate: 0.18; standard error: 0.10; p=0.08).However, the estimates were relatively consistent with those found in the main analyses in all pairs (estimate: 0.31; standard error: 0.15) and in MZ pairs only (estimate: 0.17; standard error: 0.08).These results suggest that a decrease in statistical power due to a reduction in sample size is likely to be responsible for the lack of signi cance in these associations.

Supplementary Tables
Transforming growth factor beta-1 proprotein

Fig. S1 :
Fig. S1: Overlap of samples across domains in all twin pairs, in monozygotic twin pairs only, or in dizygotic twin pairs only.

Table S1 :
Number of discordant pairs of twins out of the 257 pairs available for the analysis between the domain-speci c WPPS and the binary indicators.
legend: Number of discordant twin pairs ranged 42-94.Number of twin pairs available: 257.NA: missing values.

Table S2 :
Associations between within-pair proximity scores and discordance for multiple lifestyle legend: se: standard error.

Table S3 :
Description of variables in the proteome domain

Table S4 :
Description of variables in the metabolome domain