Home and epigenome: How DNA methylation could explain the association between housing quality and depression

Poor housing quality is a consistent risk factor for mental health problems. Despite the large body of evidence for housing’s relationship with mental health, housing quality as an environmental stressor has not yet been investigated with regards to the mediational process of DNA methylation. Previous investigations have provided little insight into the biological mechanisms through which this association may arise and been limited by insufficient control of socioeconomic status (SES) and baseline depression. By investigating the mediational role of DNA methylation in the association between housing and mental health, this research paper aimed to investigate housing’s potential as both a protectant and opportunity for intervention for mental health on a population-level. In a sample of up to 6,446 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC), we set out to investigate if housing quality (e.g. size, facilities, condensation/mould, decorations and feelings towards the home) associated with depressive symptoms (Crown Crisp Experiential Index depression scores) in early or middle adulthood (mean age 29 and 48, respectively). In these associations we controlled for neighbourhood quality, housing stability (the number of times the individual moved house in the previous 5 years), contextual risk (including socioeconomic factors such as experiences of losing a job, reduced income, homelessness) and familial history of depression (known history of persistent low mood or known diagnoses in parents). We then investigated whether this association was mediated by DNA methylation, measured at the same time points in a sub-sample of these mothers with blood sample data (n=786), whilst controlling for cell-type heterogeneity, total fat-mass, age and smoking. Housing quality predicted depression consistently over 3 years in early adulthood (beta range: .316 to 1.21, all p-values <.003), even after controlling for multiple SES risks, familial depression risk, 5-year housing stability, baseline depression at age 28 and neighbourhood quality. However, housing quality did not predict depression in middle adulthood (beta = 0.63, p value = .251). In an epigenome-wide association analysis (EWAS), housing quality was associated with DNA methylation at 4 CpG sites at age 29 with suggestive evidence for 391 CpGs, as defined in Smith et al. (2021). Following up on these 391 CpGs using high-dimensional mediational analysis, the largest indirect effect, mediating the association between housing and depression at age 29, was detected for a CpG linked to gene SLCO4A1 (beta = -.009, p-value = .052). The smallest indirect effect, mediating the association between housing and depression at age 48, was detected for a CpG linked to gene Mir_544 (beta = -.076, p-value = .037). These results demonstrate the importance of housing quality in depression’s aetiology, especially in early adulthood. However, our findings point towards limited evidence for single CpG sites mediating this association, suggesting a more complex relationship between housing quality, DNA methylation and depression. Moreover, our findings suggest the role of housing quality in the aetiology of depression may vary across the lifespan