| Title: | Liability threshold modeling of case-control status and family history of disease increases association power |
| Journal: | Nature Genetics |
| Published: | 20 Apr 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32313248/ |
| DOI: | https://doi.org/10.1038/s41588-020-0613-6 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210076 |
| Citations: | 71 (35 in last 2 years) as of 8 Aug 2024 |
Publication 5321
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Abstract
Family history of disease can provide valuable information in case-control association studies, but it is currently unclear how to best combine case-control status and family history of disease. We developed an association method based on posterior mean genetic liabilities under a liability threshold model, conditional on case-control status and family history (LT-FH). Analyzing 12 diseases from the UK Biobank (average N = 350,000) we compared LT-FH to genome-wide association without using family history (GWAS) and a previous proxy-based method incorporating family history (GWAX). LT-FH was 63% (standard error (s.e.) 6%) more powerful than GWAS and 36% (s.e. 4%) more powerful than the trait-specific maximum of GWAS and GWAX, based on the number of independent genome-wide-significant loci across all diseases (for example, 690 loci for LT-FH versus 423 for GWAS); relative improvements were similar when applying BOLT-LMM to GWAS, GWAX and LT-FH phenotypes. Thus, LT-FH greatly increases association power when family history of disease is available.</p>
5 Authors
- Margaux L. A. Hujoel
- Steven Gazal
- Po-Ru Loh
- Nick Patterson
- Alkes L. Price
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