Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.Molecular Epidemiolog

Are repressors so special after all? Specificity of negative personal events as a function of anxiety and defensiveness

Repressors have been characterized as individuals scoring high on defensiveness and low on self-reported anxiety [Weinberger, D. A., Schwartz, G. E., & Davidson, R. J. (1979). Low-anxious, high-anxious, and repressive coping styles: Psychometric patterns and behavioral and physiological responses to stress. Journal of Abnormal Psychology, 88, 369–380]. Using regression analyses, we tested whether repressors report negative personal events at reduced levels of specificity, as suggested by affect regulation accounts. Participants (N = 82) wrote brief descriptions of personal memories and imagined future experiences as prompted by emotionally negative cues. Participants rated these events for emotional intensity and importance before completing measures of defensiveness, trait anxiety and depressive symptoms. Defensiveness was associated with reduced accessibility of negative self-relevant material but, contrary to Weinberger et al.’s typology, this effect was not moderated by self-reported anxiety. Defensiveness functioned as a suppressor variable such that its inclusion in regression analyses yielded significant negative relationships between anxiety or depressive symptoms and event specificity, even though zero-order correlations between these variables and specificity were non-significant. Results suggest that research based on Weinberger et al.’s classification may underestimate the role of defensiveness in repressive coping and that researchers should consider measuring defensiveness when investigating the relationship between psychopathology and self-relevant cognition