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BackgroundDepression is a significant problem and it is vital to understand its underlying causes and related policy implications. Neighborhood characteristics are implicated in depression but the nature of this association is unclear. Unobserved or unmeasured factors may confound the relationship. This study addresses confounding in a twin study investigating neighborhood-level effects on depression controlling for genetics, common environment, and gene×environment (G × E) interactions.MethodData on neighborhood deprivation and depression were gathered from 3155 monozygotic twin pairs and 1275 dizygotic pairs (65.7% female) between 2006 and 2013. The variance for both depression and neighborhood deprivation was decomposed into three components: additive genetic variance (A); shared environmental variance (C); and non-shared environmental variance (E). Depression was then regressed on neighborhood deprivation to test the direct association and whether that association was confounded. We also tested for a G × E interaction in which the heritability of depression was modified by the level of neighborhood deprivation.ResultsDepression and neighborhood deprivation showed evidence of significant A (21.8% and 15.9%, respectively) and C (13.9% and 32.7%, respectively) variance. Depression increased with increasing neighborhood deprivation across all twins (p = 0.009), but this regression was not significant after controlling for A and C variance common to both phenotypes (p = 0.615). The G × E model showed genetic influences on depression increasing with increasing neighborhood deprivation (p < 0.001).ConclusionsNeighborhood deprivation is an important contributor to depression via increasing the genetic risk. Modifiable pathways that link neighborhoods to depression have been proposed and should serve as targets for intervention and research. [ABSTRACT FROM AUTHOR]

It has been over 5 years since the last special issue of Twin Research and Human Genetics on 'Twin Registries Worldwide: An Important Resource for Scientific Research' was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.

Major depression is a complex disorder with no single, direct causal mechanism. Morbidity has been linked to genetic processes, developmental history, and unique environmental exposures. Epigenetic mechanisms, especially DNA methylation, are also likely important factors in the pathogenesis of major depressive disorder (MDD). A community-based twin sample has many advantages for epigenetic studies, given the shared genetic and developmental histories of same-sex twin pairs. This article describes the rationale and study design for the Mood and Methylation Study in which 133 twin pairs (101 monozygotic and 32 dizygotic), both discordant and concordant for lifetime history of MDD, were evaluated on a large number of variables related to MDD. The twins also provided blood samples for an epigenome-wide association study of differentially methylated regions (DMR) relevant to MDD. Although MDD is typically considered a disorder of the central nervous system, it is unfeasible to obtain a large sample of brain tissues. However, epigenetic variation is not limited to the affected tissue but can also be detected in peripheral blood leukocytes. Thus, this study focused on monocytes for the major analyses. Additional plans for the study include gene expression analysis from the same set of twins using RNA-seq and validation of significant DMRs in postmortem brain tissues from a separate sample. Moreover, sufficient samples have been collected to perform future 'multi-omic' analyses, including metabolome, microbiome, and transcriptome. Our long-term goal is to understand how epigenomic and other 'omic' factors can be manipulated for diagnostic, preventive, and therapeutic purposes for MDD and its related conditions.

The University of Washington Twin Registry is a unique community-based registry of twin pairs who join specifically to participate in scientific research. It was founded in 2002 to serve as a resource for investigators throughout the scientific community. Current enrollment exceeds 7,200 pairs, and plans are in place to increase enrollment to 10,000 pairs by 2015. In addition to serving as a recruitment base for new research studies, the registry maintains extensive and continually expanding survey data on physical and mental health, as well as a biorepository that includes DNA from more than 8,800 individual twins. The registry is engaged in linking member data to birth records and to diagnostic and procedure variables for hospital-based care provided to members in Washington State. It also incorporates several innovative variables relevant to the built and social environments, which were created by geocoding twin addresses and linking the resulting coordinates to geospatial information systems databases. This combination of existing data and biospecimens, characterizing a group of twins who are willing to participate in research, is a valuable resource for the new wave of twin studies. These include 'omics', epigenetics, gene-by-environment interactions, and other novel methods to understand human health.