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

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posted on 2023-06-08, 22:06 authored by M K Xu, Darya GaysinaDarya Gaysina, J H Barnett, L Scoriels, L N van de Lagemaat, A Wong, M Richards, T J Croudace, P B Jones
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.

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Publication status

  • Published

File Version

  • Published version

Journal

Translational Psychiatry

ISSN

2158-3188

Publisher

Nature Publishing Group

Issue

6

Volume

5

Article number

e593

Department affiliated with

  • Psychology Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-08-13

First Open Access (FOA) Date

2015-08-13

First Compliant Deposit (FCD) Date

2015-08-13

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