Research that combines genetic and cognitive neuroscience data aims to elucidate the mechanisms that underlie human behaviour and experience by way of 'intermediate phenotypes': variations in brain function. Using neuroimaging and other methods, this approach is poised to make the transition from health-focused investigations to inquiries into cognitive, affective and social functions, including ones that do not readily lend themselves to animal models. The growing pains of this emerging field are evident, yet there are also reasons for a measured optimism.
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The authors wish to thank M. I. Posner, whose consultation contributed greatly to the conceptual direction and writing of the manuscript, and A. Gold, C. Juhasz and B. Stinson for thoughtful commentary on earlier versions of the manuscript. J.F. is presently funded by a K01 award sponsored by the National Institute of Mental Health. J.R.G. was funded by the National Science Foundation under awards REC-0634025 and DRL-0644131.
- Candidate gene
A candidate gene is a gene with a function that suggests that it might be involved in the variation observed for a particular trait. Polymorphisms in a gene that are known to alter its function (for example, through alterations in its expression) are used in candidate-gene association studies.
- Intermediate phenotype
A heritable trait or characteristic that is not a direct symptom of the condition under investigation but that has been shown to be associated with the condition. It might reflect an intermediate step in the pathway between gene and psychological function (or dysfunction). In a brain-based intermediate-phenotype approach, brain function is assayed (for example, through neuroimaging technologies) in order to measure intermediate mechanisms at a systems level.
- Linkage disequilibrium
The non-random association (that is, correlation) of alleles at two or more loci, so that certain combinations of alleles occur together more frequently than would be expected by chance. This means that a true causative locus might in fact be one that is in linkage disequilibrium with the one that is under investigation in a genetic-association study.
- Odds ratio
A measure of effect size, defined as the ratio of the odds of an event occurring in one group to the odds of it occurring in another group. In the context of a genetic-association study, this might be the odds of major depression occurring in one genotype group against the odds of it occurring in another genotype group.
The presence of two or more variants (alleles) in a gene or other DNA sequence in a population. The most commonly investigated polymorphisms are single-nucleotide polymorphism (SNPs), in which a point mutation has occurred (for example, a C base is substituted for a T base in the DNA sequence).
The design, administration and interpretation of quantitative tests for the valid and reliable measurement of psychological variables (phenotypes).
- Publication bias
The greater tendency for statistically significant results to be published (relative to non-significant results). This might be due to the unwillingness of the author to submit non-significant results, to the unwillingness of the journal to accept them, or to both. Published studies might therefore not be representative of all the studies that have been conducted.
In relation to psychological variables such as mood, a trait is the dispositional level of a particular mood or emotion (for example, trait anxiety) and reflects the mean level of the mood or emotion over time. It is usually highly correlated with the current 'state' level. More generally, a trait is a dimension along which individuals can differ in behavioural dispositions.
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Green, A., Munafò, M., DeYoung, C. et al. Using genetic data in cognitive neuroscience: from growing pains to genuine insights. Nat Rev Neurosci 9, 710–720 (2008). https://doi.org/10.1038/nrn2461
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