Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms

Abstract

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.

Keywords: Alcoholism; Brain; Chromosome band location; Gene; Genetic biomarkers; High resolution chromosome ideograms.

Fig. 1.

High resolution human chromosome ideograms (850 band level) with alcoholism gene symbols positioned at the chromosome band location. The upper ‘p’ and lower ‘q’ 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.

Fig. 1.

High resolution human chromosome ideograms (850 band level) with alcoholism gene symbols positioned at the chromosome band location. The upper ‘p’ and lower ‘q’ 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.