Mutations in human monoamine-related neurotransmitter pathway genes

Haavik, Jan; Blau, Nenad; Thöny, Beat

doi:10.1002/humu.20700

Cited by 94 publications

(83 citation statements)

References 117 publications

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“…Our analysis based on Bayesian learning algorithms revealed that ADH1B is involved in the traits identified by our PheWAS and drinking behaviors are apparently intermediary for some of them only. Although some alcohol-independent effects of ADH1B on human phenome find support in other functions for the encoded enzyme (Haavik et al, 2008), our analysis should be considered exploratory. Indeed, the WHI assessment for drinking and smoking behaviors is focused primarily on current use rather than lifetime use.…”

Section: Discussionmentioning

confidence: 99%

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

Polimanti

Kranzler

2016

Neuropsychopharmacol

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To identify novel traits associated with alleles known to predispose to alcohol and nicotine use, we conducted a phenome-wide association study (PheWAS) in a large multi-population cohort. We investigated 7688 African-Americans, 1133 Asian-Americans, 14 081 EuropeanAmericans, and 3492 Hispanic-Americans from the Women's Health Initiative, analyzing alleles at the CHRNA3-CHRNA5 locus, ADH1B, and ALDH2 with respect to phenotypic traits related to anthropometric characteristics, dietary habits, social status, psychological traits, reproductive history, health conditions, and nicotine/alcohol use. In ADH1B trans-population meta-analysis and population-specific analysis, we replicated prior associations with drinking behaviors and identified multiple novel phenome-wide significant and suggestive findings related to psychological traits, socioeconomic status, vascular/metabolic conditions, and reproductive health. We then applied Bayesian network learning algorithms to provide insight into the causative relationships of the novel ADH1B associations: ADH1B appears to affect phenotypic traits via both alcohol-mediated and alcohol-independent effects. In an independent sample of 2379 subjects, we also replicated the novel ADH1B associations related to socioeconomic status (household gross income and highest grade finished in school). For CHRNA3-CHRNA5 risk alleles, we replicated association with smoking behaviors, lung cancer, and asthma. There were also novel suggestive CHRNA3-CHRNA5 findings with respect to high-cholesterol-medication use and distrustful attitude. In conclusion, the genetics of alcohol and tobacco use potentially has broader implications on physical and mental health than is currently recognized. In particular, ADH1B may be a gene relevant for the human phenome via both alcohol metabolism-related mechanisms and other alcohol metabolismindependent mechanisms.

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Section: Discussionmentioning

confidence: 99%

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

Polimanti

Kranzler

2016

Neuropsychopharmacol

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“…MAOA and MAOB have been associated with various psychiatric disorder including depression, schizophrenia, substance abuse and Brunner syndrome. [58][59][60][61][62] The methylation levels of MAOA and MAOB were significantly elevated (1.5 and 1.4%, respectively) in BPD patients. Our results obtained in cell lines for MAOA and MAOB show that increased methylation correlates with transcriptional inactivation (Fig.…”

Section: Dna Methylation Profiling Of 14 Neuropsychiatric Genesmentioning

confidence: 99%

Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder

Dammann

Teschler²,

Haag³

et al. 2011

Epigenetics

121

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“…Candidate genes for affecting tameness and aggression In RGD, there were four genes with annotations for aggression (Tryptophan hydroxylase 1, Tph1; (Haavik et al, 2008)), fear (g-aminobutyric acid receptor subunit alpha 5, Gabra5; (Otani et al, 2005)) or anxiety (Protein kinase C-gamma, Prkcc; (Bowers et al, 2000) and plasminogen activator urokinase receptor; Plaur (Powell et al, 2003)). Two of these four genes are situated close to regions inferred to have experienced positive selection: Tph1 at 97.7 Mb and Gabra5 at 108.8 Mb.…”

Section: Search For Positive Selectionmentioning

confidence: 99%

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection

et al. 2011

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The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.

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Mutations in human monoamine-related neurotransmitter pathway genes

Cited by 94 publications

References 117 publications

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder

Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection

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