However the use of microarrays and advances in next-generation RNA-sequencing (RNA-Seq) [35] have conferred the ability to quantify mRNA transcripts in postmortem brain and analyze expression differences between alcoholics and controls within gene networks [36–39]. Genetic disorders are diagnosable conditions directly caused by genetic mutations that are inherited or occur later in life from environmental exposure. Phenotypic data were collected from MVP participants using questionnaires and the VA EHR and a blood sample was obtained for genetic analysis. Independent genetic signals from the cross-ancestry meta-analysis were searched in OpenTargets.org37 for druggability and medication target status based on their nearest genes.
Supplementary Data 45
As in EUR, AUD in AFR was genetically correlated with substance use traits including OUD, smoking trajectory (that identifies groups of individuals that follow a similar progression of smoking behavior), and maximum habitual alcohol intake. PheWAS of PRS in AFR from PsycheMERGE and Yale–Penn confirmed that AUD is genetically correlated with substance use traits. The lack of a wider set of phenotypes for comparison by ancestry is a continuing limitation. It is likely that, as for most complex diseases, alcohol dependence and AUDsare due to variations in hundreds of genes, interacting with different socialenvironments.
Supplementary Data 29
- In regions where alcohol is either prohibitively expensive or challenging to procure, there’s a noticeable reduction in alcohol problems and misuse.
- ICD-9 codes were aggregated to phecodes using the PheWAS R package to create 1812 phecodes.
- These inconsistent findings have tempered expectations and investment in both linkage and candidate gene studies.
- The observed prevalence of 12.9% for GAD is slightly higher the lifetime prevalence of 9% which has been reported for the United States [58] and the 9.1% prevalence which has been observed among people living with the human immunodeficiency virus (HIV) [59].
Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. Researchers have used both case–control and family studies to identify genes related to alcoholism risk. In addition, different strategies such genetics of alcoholism as candidate gene analyses and genome-wide association studies have been used. The strongest effects have been found for specific variants of genes that encode two enzymes involved in alcohol metabolism—alcohol dehydrogenase and aldehyde dehydrogenase.
Alcohol metabolism: How long does it stay in your system?
- Of particular value are single-nucleotide polymorphisms (SNPs)—sites at which people differ in a single base pair—in or near genes within the regions of interest.
- In addition, because heavy drinking can exacerbate age‐related physical and neurocognitive problems, interact with medications, and cause falls and accidents, especially in older adults, a longitudinal follow‐up of COGA participants aged 50 and older is in progress.
- Because alcoholism is a complex genetic disorder, the COGA researchers expected that multiple genes would contribute to the risk.
- While heredity and genetics are closely linked, they can mean different things from a medical perspective.
- These genetic variants have a high prevalence in East Asians and protect against the development of alcoholism.
COGA is an interdisciplinary project with the overarching goal of understanding the contributions and interactions of genetic, neurobiological and environmental factors towards risk and resilience over the developmental course of AUD, including relapse and recovery. In this overview, we outline the motivation behind and design of COGA as a multi‐modal project. Each of these domains has produced novel findings, highlighted in the companion reviews. However, the fundamental strength of COGA has been our ability to integrate across these domains in a cohort of families with whom we have established a robust research relationship for over three decades. Linkage studies are limited in terms of their spatial resolution, and thus, association studies that measure differences in allele frequencies between ‘case’ and ‘control’ populations were also pursued. Early association studies focused on a limited number of variants in or near genes selected a priori for their biological relevance to the trait of interest or physical location in the genome informed by prior linkage results.
- Other factors, such as friend groups and level of financial security, may be subject to change.
- Studies arerevealing other genes in which variants impact risk for alcoholism or relatedtraits, including GABRA2, CHRM2,KCNJ6, and AUTS2.
- It is likely that, as for most complex diseases, alcohol dependence and AUDsare due to variations in hundreds of genes, interacting with different socialenvironments.
- Subsequent analyses that included the additional markers supported the initial findings (Foroud et al. 2000) but did not narrow the chromosomal regions in which genes influencing alcoholism susceptibility are likely to lie.
- Despite the genetic nature of several mental disorders being illuminated, there is limited genetics data from Africa.
What does genetic risk mean?
