Authors
Emma Pruin, Yuri Milaneschi, Meike Bartels, Pietro Bassani, Brenda Penninx, Wouter Peyrot
Published in
Psychological medicine. Volume 56. Pages e326. Oct 12, 2026. Epub Oct 12, 2026.
Abstract
Genetic liability of depressive disorder can be captured by psychopathology in relatives (family history). Various methods summarize family history in a single score, differing in included information as well as the underlying model. We systematically compared the performance of family history indicators, including promising new indicators based on the liability threshold model, in predicting depressive disorder.
We calculated selected family history indicators for depression (dichotomous, proportion, novel genetically informed method - Pearson-Aitkens Family Genetic Risk Score [PAFGRS]) in 1339 participants of the Netherlands Study of Depression and Anxiety (Ncase = 1086). Polygenic scores (PGS) were computed from the most recent GWAS for major depression. We assessed correlations between genetic liability indicators, as well as their prediction of lifetime depressive disorder diagnosis.
Correlations of family history indicators with each other were high (r = 0.71-0.99) and much lower with the PGS (r = 0.15). There was a suggested increase in predictive accuracy for more elaborately computed scores, ranging from proportion to PAFGRS. The best-performing family history indicator and the PGS were independently associated with depressive disorder.
Our analysis shows that more elaborate family history indicators, including family size, prevalence, heritability, and genetic theory, would be preferable over simpler methods. Family history and PGS were complementary in prediction, showing the added value of including both in future studies.
PMID:
42861501
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.
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