| Title: | Capturing additional genetic risk from family history for improved polygenic risk prediction |
| Journal: | Communications Biology |
| Published: | 16 Jun 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35710731/ |
| DOI: | https://doi.org/10.1038/s42003-022-03532-4 |
| URL: | https://www.nature.com/articles/s42003-022-03532-4.pdf |
Publication 7413
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Abstract
Family history of complex traits may reflect transmitted rare pathogenic variants, intra-familial shared exposures to environmental and lifestyle factors, as well as a common genetic predisposition. We developed a latent factor model to quantify trait heritability in excess of that captured by a common variant-based polygenic risk score, but inferable from family history. For 941 children in the Avon Longitudinal Study of Parents and Children cohort, a joint predictor combining a polygenic risk score for height and mid-parental height was able to explain ~55% of the total variance in sex-adjusted adult height z-scores, close to the estimated heritability. Marginal yet consistent risk prediction improvements were also achieved among ~400,000 European ancestry participants for 11 complex diseases in the UK Biobank. Our work showcases a paradigm for risk calculation, and supports incorporation of family history into polygenic risk score-based genetic risk prediction models.4 Authors
- Tianyuan Lu
- Vincenzo Forgetta
- J. Brent Richards
- Celia M. T. Greenwood
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