Imaging genetics and psychiatric disorders.
Imaging genetics is an integrated research method that uses neuroimaging and genetics to assess the impact of genetic variation on brain function and structure. Imaging genetics is both a tool for the discovery of risk genes for psychiatric disorders and a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative and mechanistic aspects of brain function implicated in psychiatric disease. Early studies of imaging genetics included association analyses between brain morphology and single nucleotide polymorphisms whose function is well known, such as catechol-Omethyltransferase (COMT) and brain-derived neurotrophic factor (BDNF). GWAS of psychiatric disorders have identified genes with unknown functions, such as ZNF804A, and imaging genetics has been used to investigate clues of the biological function of these genes. The difficulty in replicating the findings of studies with small sample sizes has motivated the creation of largescale collaborative consortiums, such as ENIGMA, CHARGE and IMAGEN, to collect thousands of images. In a genome-wide association study, the ENIGMA consortium successfully identified common variants in the genome associated with hippocampal volume at 12q24, and the CHARGE consortium replicated this finding. The new era of imaging genetics has just begun, and the next challenge we face is the discovery of small effect size signals from large data sets obtained from genetics and neuroimaging. New methods and technologies for data reduction with appropriate statistical thresholds, such as polygenic analysis and parallel independent component analysis (ICA), are warranted. Future advances in imaging genetics will aid in the discovery of genes and provide mechanistic insight into psychiatric disorders.
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Hashimoto
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Ohi
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Yamamori
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Yasuda
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Fujimoto
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Umeda-Yano
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Watanabe
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M
Fukunaga
Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan. hashimor@psy.med.osaka-u.ac.jp.
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Takeda
D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D002881:Chromosomes, Human, Pair 12 / Q000737:chemistry / Q000648:ultrastructure; D003299:Cooperative Behavior; D015870:Gene Expression; D005826:Genetics, Medical / Q000295:instrumentation / Q000379:methods*; D055106:Genome-Wide Association Study; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D059906:Neuroimaging / Q000295:instrumentation / Q000379:methods*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human; C579455:BDNF protein, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase