Suchergebnisse

Abstract
Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis. We also additionally describe two longitudinal cohorts — the Brisbane Longitudinal Twin Study in Australia and the Lifelines Cohort Study in the Netherlands. By applying the methodological framework to these two unique datasets, our future research will explore the complex interplay between genetic factors, gene expression, and environmental influences on substance use behaviors and disorders across different life stages and populations.

AbstractIn this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.