Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders

Xu, M K, Gaysina, D, Barnett, J H, Scoriels, L, van de Lagemaat, L N, Wong, A, Richards, M, Croudace, T J and Jones, P B (2015) Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders. Translational Psychiatry, 5. e593. ISSN 2158-3188

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Affective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations.

Item Type: Article
Schools and Departments: School of Psychology > Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology > BF0699 Genetic psychology
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Darya Gaysina
Date Deposited: 13 Aug 2015 08:38
Last Modified: 07 Mar 2017 10:28

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