Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms.
paper
Cited
Public
- Authors
- Manzardo, Ann M; McGuire, Austen; Butler, Merlin G
- Year
- 2015
- Journal
- Gene
- PMID
- 25655461
- DOI
- 10.1016/j.gene.2015.01.064
- PMCID
- PMC6675570
OBJECTIVE: Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence. METHOD: We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form. RESULTS: We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG). CONCLUSIONS: High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism gene(s) at the chromosome band level to guide research, diagnosis, and treatment. Chromosome ideograms may facilitate gene-based personalized counseling of alcohol dependent individuals and their families.
High resolution human chromosome ideograms (850 band level) with alcoholism gene symbols positioned at the chromosome band location. The upper βpβ and lower βqβ arms for each chromosome are separated by the centromere area highlighted in black. The gene symbol in alphabetical order, expanded name of the gene and precise chromosome band position are found in Table 1.
1β14 of 14
| Name | Type |
|---|---|
| Aberrant behavioral disorders local | phenotype |
| Abuse behaviors local | phenotype |
| acetaldehyde | drug |
| Addiction-related brain regions local | anatomy |
| ADH | gene |
| ADH1B | gene |
| ADH1C | gene |
| age at initiation | phenotype |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcohol dependence | phenotype |
| alcoholism | phenotype |
| alcoholism-related phenotypes local | phenotype |
| Alcoholism vulnerability local | phenotype |
| Alcohol-responsive brain networks local | anatomy |
| alcohol sensitivity | phenotype |
| ALDH2 | gene |
| AUTS2 | gene |
| Bdnf | gene |
| Biomarkers local | variant |
| brain | anatomy |
| brain function | phenotype |
| brain growth and development local | phenotype |
| brain structure | anatomy |
| CDH13 | gene |
| cirrhotic liver disease local | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| COMT | gene |
| consumption | phenotype |
| copy number variation | variant |
| craving | phenotype |
| DNA | drug |
| dopamine | drug |
| DRD2 | gene |
| drinking | phenotype |
| EFNA5 | gene |
| ethanol consumption | phenotype |
| event-related potential | phenotype |
| Families with a history of alcoholism local | cohort |
| Families without a history of alcoholism local | cohort |
| GABA | phenotype |
| Gabra1 | gene |
| GABRA2 | gene |
| GAD1 | gene |
| gene biomarkers local | gene |
| Genes associated with alcoholism local | gene |
| Genetic biomarkers local | gene |
| genetic variants | cohort |
| genomic imprinting local | variant |
| glutamate | drug |
| GRIK3 | gene |
| GRIN2C | gene |
| Htr1b | gene |
| Htr3a | gene |
| Htr3b | gene |
| human brain | anatomy |
| level of response to alcoholβs effects local | phenotype |
| MAOA | gene |
| nutritional deficiency | phenotype |
| opioid receptor | drug |
| Oprd1 | cohort |
| OPRM1 | cohort |
| prefrontal cortex | anatomy |
| primary disease risk local | phenotype |
| psychiatric disorders | phenotype |
| regions of homozygosity local | variant |
| Reward processing regions local | anatomy |
| SAGE | cohort |
| segmental deletions local | variant |
| segmental duplications | variant |
| serotonin | drug |
| Slc1a3 | gene |
| SLC5A11 local | gene |
| SLC6A4 | gene |
| smoking status | phenotype |
| tolerance | phenotype |
| uniparental disomy | variant |
| Withdrawal sensitivity local | phenotype |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| The genetic epidemiology of substance use disorder: A review. | 2017 | 28938182 |
External
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| Integrative Genomics Approach Identifies Glial Transcriptomic Dysregulation and Risk in the Cortex of Individuals With Alcohol Use Disorder. | Warden AS et al. | β | 2026 | β |
| Bibliometric Insights in Genetic Factors of Substance-Related Disorders: Intellectual Developments, Turning Points, and Emerging Trends. | Wang K et al. | β | 2021 | β |
| Morphopathological approaches in alcoholism. | DrΔgoi AM et al. | β | 2020 | β |
| Medication-enhanced behavior therapy for alcohol use disorder: Naltrexone, Alcoholics Anonymous Facilitation, and OPRM1 genetic variation. | Stewart SH et al. | β | 2019 | β |
| The genetic epidemiology of substance use disorder: A review. | Prom-Wormley EC et al. | β | 2017 | β |
| A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction. | Bell RL et al. | β | 2016 | β |
| GABBR1 and SLC6A1, Two Genes Involved in Modulation of GABA Synaptic Transmission, Influence Risk for Alcoholism: Results from Three Ethnically Diverse Populations. | Enoch MA et al. | β | 2016 | β |
| White matter disruptions in male cocaine polysubstance users: Associations with severity of drug use and duration of abstinence. | van Son D et al. | β | 2016 | β |
| Further analyses support the association between light eye color and alcohol dependence. | Sulovari A et al. | β | 2015 | β |
| [Genius between music and disease: Medical considerations on Ludwig van Beethoven]. | Gasenzer ER et al. | β | 2015 | β |
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