A neurogenetics approach to understanding individual differences in brain, behavior, and risk for psychopathology

被引:59
作者
Bogdan, R. [1 ]
Hyde, L. W. [2 ,3 ]
Hariri, A. R. [1 ,4 ]
机构
[1] Duke Univ, Dept Psychol & Neurosci, Lab NeuroGenet, Durham, NC 27705 USA
[2] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA
[3] Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA
[4] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27705 USA
关键词
epigenetics; epistasis; GWAS; GxE; multilocus; neurogenetics; GENOME-WIDE ASSOCIATION; CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENOTYPE; GENE-ENVIRONMENT INTERACTIONS; MAJOR DEPRESSIVE DISORDER; STRESSFUL LIFE EVENTS; ANXIETY-LIKE BEHAVIOR; GLUCOCORTICOID-RECEPTOR; QUANTITATIVE TRAIT; AMYGDALA ACTIVATION;
D O I
10.1038/mp.2012.35
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neurogenetics research has begun to advance our understanding of how genetic variation gives rise to individual differences in brain function, which, in turn, shapes behavior and risk for psychopathology. Despite these advancements, neurogenetics research is currently confronted by three major challenges: (1) conducting research on individual variables with small effects, (2) absence of detailed mechanisms, and (3) a need to translate findings toward greater clinical relevance. In this review, we showcase techniques and developments that address these challenges and highlight the benefits of a neurogenetics approach to understanding brain, behavior and psychopathology. To address the challenge of small effects, we explore approaches including incorporating the environment, modeling epistatic relationships and using multilocus profiles. To address the challenge of mechanism, we explore how non-human animal research, epigenetics research and genome-wide association studies can inform our mechanistic understanding of behaviorally relevant brain function. Finally, to address the challenge of clinical relevance, we examine how neurogenetics research can identify novel therapeutic targets and for whom treatments work best. By addressing these challenges, neurogenetics research is poised to exponentially increase our understanding of how genetic variation interacts with the environment to shape the brain, behavior and risk for psychopathology. Molecular Psychiatry (2013) 18, 288-299; doi:10.1038/mp.2012.35; published online 22 May 2012
引用
收藏
页码:288 / 299
页数:12
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