Some, such as SNCA, CPE, DRD2 and GRM3, have weaker evidence based on the GWAS data but strong independent evidence in terms of gene expression studies and other prior human or animal genetic work. Whereas we cannot exclude that more recently discovered genes have had less hypothesis-driven work performed and thus might score lower on CFG, it is to be noted that the CFG approach integrates predominantly non-hypothesis-driven, discovery-type data sets, such as GWAS data, linkage, quantitative traits loci and, particularly, gene expression. We also cap each line of evidence from an experimental approach (Figure 1), to minimize any ‘popularity’ bias, whereas multiple studies of the same kind are conducted on better-established genes. In the end, it is gene-level reproducibility across multiple approaches and platforms that is built into the approach and gets prioritized most by CFG scoring during the discovery process. Our top results subsequently show good reproducibility and predictive ability in independent cohort testing, the litmus test for any such work.
Supplementary Data 21
- Chromosome ideograms may facilitate gene-based personalized counseling of alcohol dependent individuals and their families.
- Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive.
- Of these, 277,531 individuals had two or more separate encounters in the VA Healthcare System in each of the 2 years prior to enrollment in MVP, consisting of 21,209,658 records.
- The previous COGA studies have provided critical information to better understand the genetic and biological underpinnings of AUD.
- Just as risk factors increase your chance of experiencing a condition, protective factors lower your risk.
It has not escaped our attention that other ways of weighing the lines of evidence may give slightly different results in terms of prioritization, if not in terms of the list of genes per se. https://ecosoberhouse.com/ Nevertheless, we think this simple scoring system provides a good separation of genes, with specificity provided by human data and sensitivity provided by animal model data. Twin and adoption studies have shown that half of the risk of alcohol dependence, a subtype of AUD, is heritable9. The single-nucleotide polymorphism (SNP) heritability of alcohol dependence in a family-based, European-American (EA) sample was 16%10 and 22% in an unrelated African-American (AA) sample11. In the meta-analysis of data from the UK Biobank (UKBB) and 23andMe, the SNP heritability of the total AUDIT was estimated to be 12%, while for the AUDIT-C and AUDIT-P it was 11% and 9%, respectively).
Links to NCBI Databases
- This review describes the genetic approaches and results from the family‐based Collaborative Study on the Genetics of Alcoholism (COGA).
- To compare within- and cross-ancestry fine mapping, we performed within-ancestry fine mapping for the above 92 regions using the same SNP sets and EUR-only LD information (Fig. 2b,c).
- One such successful study performed exon-focused sequencing of impulsive individuals derived from a Finnish population isolate and identified a stop codon in HTR2B (1% frequency) that was unique to Finns.
A GWAS of AUD that included AUDIT-C as alcoholism and genetics a covariate identified five GWS loci in EAs and one in AAs (Supplementary Data 8). Among EAs, four of the loci were the same as for AUD, the only non-overlapping finding being DIO1 (Iodothyronine Deiodinase 1). In AAs, ADH1B remained significant for AUD when accounting for AUDIT-C, but TSPAN5 did not. We differentiated participants genetically into five populations (see Methods, Supplementary Fig. 1) and removed outliers. There was a high degree of concordance (Supplementary Fig. 2) between the genetically defined populations and the self-reported groups for European Americans (EAs, 95.6% were self-reported Non-Hispanic white) and African Americans (AAs, 94.5% were self-reported Non-Hispanic black).
Is There an Alcohol Addiction Gene?
Because he is a member of a support group that stresses the importance of anonymity at the public level, he does not use his photograph or his real name on this website. Your socioeconomic status is made up of economic and societal factors such as your income, level of education, employment, location of residence, and available resources. That doesn’t mean you’ll absolutely develop AUD if you have a family member living with the condition. You may have a higher genetic predisposition, but the underlying causes of AUD are multifaceted and complex.
- COGA was designed during the linkage era to identify genes affecting the risk for alcohol use disorder (AUD) and related problems, and was among the first AUD-focused studies to subsequently adopt a genome-wide association (GWAS) approach.
- One of the few other GWAS with a significant result was a meta-analysis of an alcohol consumption phenotype in 26,316 individuals from 12 European ancestry population based samples with replication genotyping in another 21,185 individuals that found a genome-wide significant result for one SNP in the autism susceptibility candidate gene 2 (AUTS2) 69.
- A review of studies from 2020, which looked at a genome-wide analysis of more than 435,000 people, found 29 different genetic variants that increased the risk of problematic drinking.
- Scientists have learned through studies of identical and non-identical twins that alcohol use disorder is heritable, with genetic factors accounting for about half of the risk of alcohol dependence.
- “Mutation or not, I urge anyone wanting to consume alcohol to consider both the quality and quantity of their drinks.”
- AUD isn’t directly caused by genetics, but genetics may predispose you to developing AUD later in life.
Supplementary Data 41
Abundant evidence indicates thatalcoholism is a complex genetic disease, with variations in a large number ofgenes affecting risk. Some of these genes have been identified, including twogenes of alcohol metabolism, ADH1B and ALDH2,that have the strongest known affects on risk for alcoholism. Studies arerevealing other genes in which variants impact risk for alcoholism or relatedtraits, including GABRA2, CHRM2,KCNJ6, and AUTS2. As larger samples areassembled and Alcoholics Anonymous more variants analyzed, a much fuller picture of the many genesand pathways that impact risk will be discovered.
- An item-level study of the AUDIT questionnaire confirmed a two-factor structure at the genetic level, underscoring unique genetic influences on alcohol consumption and alcohol-related problems14 and noted that the genetics of drinking frequency were confounded by socioeconomic status.
- Alcohol use disorder (AUD) is a diagnosis once referred to as “alcoholism.” It’s a condition characterized by patterns of excessive alcohol misuse despite negative consequences and major distress in important areas of daily function.
- Alcohol addiction is a serious issue that impacts not only individuals but also their family members and society.
- Commonly, genome wide association studies (GWAS) of alcoholism have focused on phenotypes based on the Diagnostic & Statistical Manual of Mental Disorders (DSM)14.
- Genetic variation in neurobiological pathways, including stress-response systems, may influence vulnerability to the development of permanent neurological changes in response to heavy alcohol use.
- BOLT-LMM65 was used to correct for relatedness, with age, sex and the first ten PCs as covariates.
Core Resource information on genetic vulnerability to AUD
The median number of SNPs in the credible sets was 13, with 7 credible sets containing a single variant and 26 containing ≤5 variants, indicating that cross-ancestry fine mapping improved causal variant identification, consistent with other studies reporting improved fine mapping by including other ancestries12. The AUDIT consists of ten multiple-choice questions to assess your behaviors regarding alcohol consumption. It assesses three areas, including alcohol intake, potential for dependence, and whether you have experienced harm related to alcohol consumption. The researchers believe that even larger studies may help to differentiate the genetics behind alcohol addiction. But the ability to tap into “big data” such as 23andMe’s research cohort as well as the UK Biobank, which Palmer and his team used for this study, has opened up new research opportunities for those studying behavioral traits — like addiction and substance abuse — as well as neuropsychiatric conditions and personality.
