ArticleEuropean journal of human genetics : EJHG2015
Homogeneous case subgroups increase power in genetic association studies.
Article in European journal of human genetics : EJHG, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
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- A polygenic risk score analysis of ASD and ADHD across emotion recognition subtypes.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2021Article
- Phenotypic and genetic markers of psychopathology in a population-based sample of older adults.Translational psychiatry · 2021Article
- Prediction of Early Childhood Caries Based on Single Nucleotide Polymorphisms Using Neural Networks.Genes · 2021Article
- Genetic Epidemiology of Complex Phenotypes.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Clustering by phenotype and genome-wide association study in autism.Translational psychiatry · 2020Article
- Identification of clinically relevant phenotypes in patients with Ebstein anomaly.Clinical cardiology · 2018Observational
- Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.Biological psychiatry · 2017Article
- Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review.Psychopathology review · 2017Article
- The stability and change of etiological influences on depression, anxiety symptoms and their co-occurrence across adolescence and young adulthood.Psychological medicine · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies of clinically defined cases against controls have transformed our understanding of the genetic causes of many diseases. However, there are limitations to the simple clinical definitions used in these studies, and GWAS analyses are beginning to explore more refined phenotypes in subgroups of the existing data sets. These analyses are often performed ad hoc without considering the power requirements to justify such analyses. Here we derive expressions for the relative power of such subgroup analyses and determine the genotypic relative risks (GRRs) required to achieve equivalent power to a full analysis for relevant scenarios. We show that only modest increases in GRRs may be required to offset the reduction in power from analysing fewer cases, implying that analyses of more genetically homogenous case subgroups may have the potential to identify further associations. We find that, for lower genotypic relative risks in the full sample, subgroup analyses of more homogeneous cases have relatively more power than for higher index genotypic relative risks and that this effect is stronger for rare as opposed to common variants. As GWA studies are likely to have now identified the majority of SNPs with stronger effects, these results strongly advocate a renewed effort to identify phenotypically homogeneous disease groups, in which power to detect genetic variants with small effects will be greater. These results suggest that analysis of case subsets could be a powerful strategy to uncover some of the hidden heritability for common complex disorders, particularly in identifying rarer variants of modest effect.
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