Is Alcoholism Hereditary or Genetic?

Human studies

Reproducibility of findings across different studies, experimental paradigms and technical platforms is deemed more important (and scored as such by CFG) than the strength of finding in an individual study (for example, P-value in a GWAS). While there is overlap between alcohol use disorder and alcohol consumption, the researchers did further analysis and found a “distinct genetic architecture” differentiating alcohol abuse from alcohol consumption. And these distinctions will be important for identifying the genetics of addiction, the researchers said. The first involves focusing the testing on specific genes that are selected on the basis of their physiological roles or their reported involvement in related traits. These so-called candidate gene studies have been fruitful in alcohol research.

Collaborative Study on the Genetics of Alcoholism (COGA)

A standard drink is defined in the US as 12ounces of beer, 5 ounces of wine or 1.5 ounces of spirits, all of which approximate14 g of pure ethanol).

This offers an alternative explanation for the opposite genetic associations38, particularly in an older clinical sample in which a large proportion report current abstinence (reflected in an AUDIT-C score of 0).

For studies of rare variants, families are quite valuable for sortingout true positives from the background of individual variations that we allharbor.

For this complex set of genetic associations to be useful in informing clinical recommendations on safe levels of alcohol consumption, it will be necessary to elucidate the mechanisms underlying these findings.

Beyond that, Palmer and his team want to develop a better understand of how the genes they’ve identified might influence these traits, but using animal and cellular models.

One way around this has been the use of intermediate phenotypes, including electrophysiological and imaging, that reflect mediating factors in behavior and are likely to be influenced by variation at fewer genes.

During your dreams, the brain also processes memories, which explains why the association with drinking in the dream might feel so realistic.

ICD-9 codes were aggregated to phecodes using the PheWAS R package to create 1812 phecodes. To improve the specificity of these codes, individuals with at least two instances of the phecode were considered cases, those with no instance of the phecode controls, and those with one instance of a phecode or a related phecode as other. A PheWAS using logistic regression models with either AUDIT-C or AUD PRS as the independent variable, phecodes as the dependent variables, and age, sex and the first five PCs as covariates were used to identify secondary phenotypic associations. A phenome-wide significance threshold of 2.96 × 10−5 was applied to account for multiple testing. We also conducted PheWAS in Yale–Penn, a deeply phenotyped cohort with comprehensive psychiatric assessments (SUDs and psychiatric disorders) and assessments for physical and psychosocial traits28.

What are the protective factors for AUD?

However, sex-stratified GWAS also identified two female-specific signals for AUDIT-C (Supplementary Data 3, Supplementary Figs. 9, 10) and one for AUD (Supplementary Data 4, Supplementary Figs. 11, 12).

Thus it is not surprising that diseases of the GI system,including cirrhosis, pancreatitis, and cancers of the upper GI tract are affected byalcohol consumption80-86.

Your genetics can influence how likely you are to develop AUD, but there’s currently no evidence of a specific gene that directly causes AUD once you start drinking.

When both types of studies point to the same genes, however, it provides additional evidence for the involvement of these genes. Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. However, identifying those genes and the specific variations involved is challenging. Researchers have used both case–control and family studies to identify genes related to alcoholism risk. In addition, different strategies such 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.

While recovery dreams play out relapses, they are not necessarily indicative that someone will drink or break their sobriety. These dreams can induce feelings of shame, guilt, or panic about relapsing upon waking. The iPSYCH21,22 samples were selected from a baseline birth cohort Halfway house comprising all singletons born in Denmark between 1 May 1981 and 31 December 2008. MVP is a biobank supported by the United States Department of VA with rich phenotypic data collected using questionnaires and the VA electronic health record system. These findings are important for researchers because of similar overlap with other addictive behavior, said lead researcher Prof. Abraham Palmer. Howard J. Edenberg, Ph.D, is a Distinguished Professor and Chancellor’s Professor in the Department of Biochemistry and Molecular Biology and the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana.

Supplementary Data 2

In AAs, EIF4E, ADH4, and METAP1 are GWS for AUD, while ADGRB2 is the only GWS locus in LAs. To elucidate further the genetic differences between AUDIT-C and AUD, we conducted a GWAS of each phenotype with the other phenotype as a covariate. A GWAS of AUDIT-C with AUD as a covariate identified 10 GWS loci in EAs and 2 GWS loci in AAs (Supplementary Data 7). In both EAs and AAs, all loci overlapped with the GWS findings for AUDIT-C alone. A GWAS of AUD that included AUDIT-C as 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).

Links to NCBI Databases

The nominally higher SNP heritability in females than males could be due to the substantially smaller size of the female subsample.

The drawback to this approach isthat linkage studies find broad regions of the genome, often containing manyhundreds of genes.

The test cohort 2 data were used to test for epistatic interactions among the best P-value SNPs in the 11 top candidate genes from our work.

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.

In summary, GWASs have been limited by difficulties in quantifying alcohol-related phenotypes and in obtaining large sample sizes, together with co-morbidity of alcoholism with other behavioral and neuropsychiatric disorders, gender effects and population admixture.

Other top candidate genes https://ecosoberhouse.com/ in the panel (MOBP, MBP and MOG) are involved in myelination (Table 3). They are decreased in expression in the prefrontal cortex of human alcoholics, as well as in our stress-reactive DBP animal model of alcoholism, before exposure to any alcohol. Interestingly, MOBP and MBP are increased in expression in the amygdala in the DBP mice, opposite to the direction of change in the PFC, consistent with a frontal deactivation and a limbic hyperactivity, which could lead to impulsivity. GFAP (glial fibrillary acidic protein), a top candidate gene with a CFG score of 9.5, is an astrocyte intermediate filament-type protein involved in neuron–astrocyte interactions, cell adhesion, process formation and cell–cell communication.