Genetic analyses benefit from using less heterogeneous phenotypes: an illustration with the hospital anxiety and depression scale (HADS).
作者： Charles A. Laurin , Jouke-Jan Hottenga , Gonneke Willemsen , Dorret I. Boomsma , Gitta H. Lubke
DOI: 10.1002/GEPI.21897
关键词:
摘要: Phenotypic heterogeneity of depression has been cited as one the causes limited success to detect genetic variants in genome-wide studies. The 7-item Hospital Anxiety and Depression Scale (HADS-D) was developed individuals with physical health problems. An initial psychometric analysis showed that a short version ("HADS-4") is less heterogeneous hence more reliable than full scale, correlates equally strong DSM-oriented scale. We compared HADS-D HADS-4 assess benefits using phenotype measures analyses. three separate analyses: (1) twin- family-based heritability estimation, (2) SNP-based estimation software GCTA, (3) association study (GWAS). twin resulted estimates between 18% 25%, additive variance being largest component. There also evidence for assortative mating dominance component variance, having slightly lower assortment. Importantly, when estimating from SNPs, did not show significant component, while HADS-4, statistically amount estimated. Moreover, had substantially SNPs small P-values GWAS HADS-D. Our results underline homogeneous phenotypes psychiatric Homogeneity can be increased by focusing on core symptoms disorders, thus reducing noise aggregate caused different symptom profiles.
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