Recent advances in the study of alcoholism have thrown light on the involvement of various neurotransmitters in the phenomenon of alcohol addiction. Various neurotransmitters have been implicated in alcohol addiction due to their imbalance in the brain, which could be either due to their excess activity or inhibition. This review paper aims to consolidate and to summarize some of the recent papers which have been published in this regard. The review paper will give an overview of the neurobiology of alcohol addiction, followed by detailed reviews of some of the recent papers published in the context of the genetics of alcohol addiction. Furthermore, the author hopes that the present text will be found useful to novices and experts alike in the field of neurotransmitters in alcoholism.
BackgroundOne explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i.e. human-specific differentially methylated regions (DMRs). We used analytical tools that evaluate polygenic enrichment of a subset of genomic variants against all variants.ResultsSchizophrenia was the only trait in which DMR SNPs showed clear enrichment of association that passed the genome-wide significance threshold. The enrichment was not observed for Neanderthal or Denisovan DMRs. The enrichment seen in human DMRs is comparable to that for genomic regions tagged by Neanderthal Selective Sweep markers, and stronger than that for Human Accelerated Regions. The enrichment survives multiple testing performed through permutation (n = 10,000) and bootstrapping (n = 5000) in INRICH (p < 0.01). Some enrichment of association with height was observed at the gene level.ConclusionsRegions where DNA methylation modifications have changed during recent human evolution show enrichment of association with schizophrenia and possibly with height. Our study further supports the hypothesis that genetic variants conferring risk of schizophrenia co-occur in genomic regions that have changed as the human species evolved. Since methylation is an epigenetic mark, potentially mediated by environmental changes, our results also suggest that interaction with the environment might have contributed to that association.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1177-2) contains supplementary material, which is available to authorized users.
Major mental disorders are highly prevalent and make a substantial contribution to the global disease burden. It is known that mental disorders share clinical characteristics, and genome-wide association studies (GWASs) have recently provided evidence for shared genetic factors as well. Genetic overlaps are usually identified at the single-marker level. Here, we aimed to identify genetic overlaps at the gene level between 7 mental disorders (schizophrenia, autism spectrum disorder, major depressive disorder, anorexia nervosa, ADHD, bipolar disorder and anxiety), 8 brain morphometric traits, 2 cognitive traits (educational attainment and general cognitive function) and 9 personality traits (subjective well-being, depressive symptoms, neuroticism, extraversion, openness to experience, agreeableness and conscientiousness, children’s aggressive behaviour, loneliness) based on publicly available GWASs. We performed systematic conditional regression analyses to identify independent signals and select loci associated with more than one trait. We identified 48 genes containing independent markers associated with several traits (pleiotropy at the gene level). We also report 9 genes with different markers that show independent associations with single traits (allelic heterogeneity). This study demonstrates that mental disorders and related traits do show pleiotropy at the gene level as well as the single-marker level. The identification of these genes might be important for prioritizing further deep genotyping, functional studies, or drug targeting.
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