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2.6 - Genetic Association Studies and Neurotransmitter Pathways

from 2 - Neurotransmitters and Receptors

Published online by Cambridge University Press:  08 November 2023

By
Jack F. G. Underwood  and
Jeremy Hall
Edited by
Mary-Ellen Lynall ,
Peter B. Jones  and
Stephen M. Stahl
Mary-Ellen Lynall
Affiliation:
University of Cambridge
Peter B. Jones
Affiliation:
University of Cambridge
Stephen M. Stahl
Affiliation:
University of California, San Diego
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Summary

Over the past 50 years, genomic methodologies have paved the way to a greater understanding of the underlying pathology of mental health disorders. In that time the techniques have developed from candidate gene studies in relatively small samples of patients, to large-scale collaborative studies using array and DNA sequencing approaches. These methodological approaches are outlined in detail in Chapter 7. In particular, genome-wide association studies (GWAS), which examine the association between single-nucleotide polymorphisms (SNPs) and disease, have made great inroads into our understanding of genetic risk for mental health disorders. While SNPs can be used to investigate any part of the genome, here we focus on what they have taught us about the role of neurotransmitter systems in psychiatry.

Type
Chapter
Information
Cambridge Textbook of Neuroscience for Psychiatrists , pp. 41 - 44
Publisher: Cambridge University Press
Print publication year: 2023

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References

Howard, DM, Adams, MJ, Clarke, T-K et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22:343–352.CrossRefGoogle ScholarPubMed
Wray, NR, Ripke, S, Mattheisen, M et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018; 50:668–681.CrossRefGoogle ScholarPubMed
Ripke, S, Neale, BM, Corvin, A et al. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427.Google Scholar
Trubetskoy, V, Pardiñas, AF, Qi, T et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022;604(7906):502–508.CrossRefGoogle ScholarPubMed
Mullins, N, Forstner, AJ, O’Connell, KS, Coombes, B, Coleman, JRI, Qiao, Z et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet. 2021;53(6):817–829.CrossRefGoogle Scholar
Consortium TN and PAS of the PG, O’Dushlaine, C, Rossin, L et al. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat Neurosci. 2015;18:199–209.Google Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013;381:1371–1379.CrossRefGoogle Scholar
Craddock, N, Sklar, P. Genetics of bipolar disorder. Lancet. 2013;381:1654–1662.CrossRefGoogle ScholarPubMed
Power, RA, Tansey, KE, Buttenschøn, HN et al. Genome-wide association for major depression through age at onset stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Biol Psychiatry. 2017;81:325–335.CrossRefGoogle Scholar
Howes, O, McCutcheon, R, Stone, J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J Psychopharmacol. 2015;29:97–115.CrossRefGoogle Scholar
Laruelle, M, Kegels, M, Kegeles, LS, Abi-Dargham, A. Glutamate, dopamine, and schizophrenia. Ann N Y Acad Sci. 2003;1003:138–158.CrossRefGoogle ScholarPubMed
Kesby, J, Eyles, D, McGrath, J, Scott, J. Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience. Transl Psychiatry. 2018;8:30.CrossRefGoogle ScholarPubMed
Sekar, A, Bialas, AR, de Rivera, H et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177–183.CrossRefGoogle ScholarPubMed
Owens, MJ, Nemeroff, CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 1994;40:288–295.CrossRefGoogle ScholarPubMed
Stahl, SM. Mechanism of action of serotonin selective reuptake inhibitors: serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord. 1998;51:215–235.CrossRefGoogle ScholarPubMed
Faraone, SV, Larsson, H. Genetics of attention deficit hyperactivity disorder. Mol Psychiatry. 2019;24:562–575.CrossRefGoogle ScholarPubMed
Thapar, A, Martin, J, Mick, E et al. Psychiatric gene discoveries shape evidence on ADHD’s biology. Mol Psychiatry. 2016;21:1202–1207.CrossRefGoogle ScholarPubMed
Demontis, D, Walters, RK, Martin, J et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet. 2019;51:63–75.CrossRefGoogle ScholarPubMed
Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium, Consortium TASDWG of TPG. Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol Autism. 2017;8:21.CrossRefGoogle Scholar

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