title: Molecular mechanisms underlying noncoding risk variations in psychiatric genetic studies.
abstract: Recent large-scale genetic approaches such as genome-wide association studies have allowed the identification of common genetic variations that contribute to risk architectures of psychiatric disorders. However, most of these susceptibility variants are located in noncoding genomic regions that usually span multiple genes. As a result, pinpointing the precise variant(s) and biological mechanisms accounting for the risk remains challenging. By reviewing recent progresses in genetics, functional genomics and neurobiology of psychiatric disorders, as well as gene expression analyses of brain tissues, here we propose a roadmap to characterize the roles of noncoding risk loci in the pathogenesis of psychiatric illnesses (that is, identifying the underlying molecular mechanisms explaining the genetic risk conferred by those genomic loci, and recognizing putative functional causative variants). This roadmap involves integration of transcriptomic data, epidemiological and bioinformatic methods, as well as in vitro and in vivo experimental approaches. These tools will promote the translation of genetic discoveries to physiological mechanisms, and ultimately guide the development of preventive, therapeutic and prognostic measures for psychiatric disorders.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: H
authors.initials: H
authors.lastname: Chang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.
authors.forename: M
authors.identifier: 0000-0002-8197-6552
authors.initials: M
authors.lastname: Li
mesh_terms: D021901:DNA, Intergenic / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D016678:Genome / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D008603:Mental Health; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D021901:DNA, Intergenic