ArticleAmerican journal of human genetics2022
Accounting for age of onset and family history improves power in genome-wide association studies.
Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetics of age-at-onset in major depression.Translational psychiatry · 2022Pooled it
- LT-FGRS: a unifying R-package for the estimation of family-based genetic liabilities at population-scale.bioRxiv : the preprint server for biology · 2026Article
- PEStimate: predicting offspring disease risk after polygenic embryo screening.Bioinformatics (Oxford, England) · 2026Article
- Exposure accumulation drives age-dependent disease architectures and polygenic risk scores.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Genetic analyses of eight complex diseases using predicted continuous representations of disease.Cell reports methods · 2025Article
- Automatic detection of n-degree family members.Frontiers in genetics · 2025Article
- A cautionary tale for Alzheimer's disease GWAS by proxy.Nature genetics · 2024Article
- Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.Nature genetics · 2024Article
- Genetic liability estimated from large-scale family data improves genetic prediction, risk score profiling, and gene mapping for major depression.American journal of human genetics · 2024Article
- Using Alternative Definitions of Controls to Increase Statistical Power in GWAS.Behavior genetics · 2024Article
- Human-specific insights into candidate genes and boosted discoveries of novel loci illuminate roles of neuroglia in reading disorders.Genes, brain, and behavior · 2024Article
- Rare copy-number variants as modulators of common disease susceptibility.Genome medicine · 2024Article
- Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies.Molecular psychiatry · 2023Review
- Phenotype integration improves power and preserves specificity in biobank-based genetic studies of major depressive disorder.Nature genetics · 2023Article
- ADuLT: An efficient and robust time-to-event GWAS.Nature communications · 2023Article
- Genetic insights into the age-specific biological mechanisms governing human ovarian aging.American journal of human genetics · 2023Article
- Age of onset and cumulative risk of mental disorders: a cross-national analysis of population surveys from 29 countries.The lancet. Psychiatry · 2023Article
- Germline mechanisms of immunotherapy toxicities in the era of genome-wide association studies.Immunological reviews · 2023Review
- Leveraging family history in genetic association analyses of binary traits.BMC genomics · 2022Article
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21 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age of onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Here, we present LT-FH++, an extension of the liability threshold model conditioned on family history (LT-FH), which jointly accounts for age of onset and sex as well as family history. Using simulations, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields statistically significant power gains over LT-FH and large power gains over genome-wide association study by proxy (GWAX). We applied our method to four psychiatric disorders available in the iPSYCH data and to mortality in the UK Biobank and found 20 genome-wide significant associations with LT-FH++, compared to ten for LT-FH and eight for a standard case-control GWAS. As more genetic data with linked electronic health records become available to researchers, we expect methods that account for additional health information, such as LT-FH++, to become even more beneficial.
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