ArticleAmerican journal of human genetics2016
Disease and Polygenic Architecture: Avoid Trio Design and Appropriately Account for Unscreened Control Subjects for Common Disease.
Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 5 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Sex-stratified genome-wide association meta-analysis of major depressive disorder.Nature communications · 2025Pooled it
- Pervasive Downward Bias in Estimates of Liability-Scale Heritability in Genome-wide Association Study Meta-analysis: A Simple Solution.Biological psychiatry · 2023Pooled it
- Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism.Translational psychiatry · 2020Pooled it
- Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium.Biological psychiatry · 2018Pooled it
- Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Molecular autism · 2017Pooled it
- Genetic architectures of brain-related traits are shaped by strong selective constraints.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Estimating disorder probability based on polygenic prediction using the BPC approach.Nature communications · 2025Article
- Polygenic and developmental profiles of autism differ by age at diagnosis.medRxiv : the preprint server for health sciences · 2025Article
- Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.Molecular psychiatry · 2025Review
- The genetic architecture of youth anxiety: a study protocol.BMC psychiatry · 2024Article
- Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants.American journal of human genetics · 2023Article
- Investigating Direct and Indirect Genetic Effects in Attention-Deficit/Hyperactivity Disorder Using Parent-Offspring Trios.Biological psychiatry · 2023Article
- Genetic correlates of phenotypic heterogeneity in autism.Nature genetics · 2022Article
- Polygenic risk scores of endo-phenotypes identify the effect of genetic background in congenital heart disease.HGG advances · 2022Article
- Integrated analysis of direct and proxy genome wide association studies highlights polygenicity of Alzheimer's disease outside of the APOE region.PLoS genetics · 2022Article
- How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID).Journal of eating disorders · 2022Review
- Exploring the genetic heterogeneity in major depression across diagnostic criteria.Molecular psychiatry · 2021Article
- Article
- Analysis of genetic differences between psychiatric disorders: exploring pathways and cell types/tissues involved and ability to differentiate the disorders by polygenic scores.Translational psychiatry · 2021Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) are an optimal design for discovery of disease risk loci for diseases whose underlying genetic architecture includes many common causal loci of small effect (a polygenic architecture). We consider two designs that deserve careful consideration if the true underlying genetic architecture of the trait is polygenic: parent-offspring trios and unscreened control subjects. We assess these designs in terms of quantification of the total contribution of genome-wide genetic markers to disease risk (SNP heritability) and power to detect an associated risk allele. First, we show that trio designs should be avoided when: (1) the disease has a lifetime risk > 1%; (2) trio probands are ascertained from families with more than one affected sibling under which scenario the SNP heritability can drop by more than 50% and power can drop as much as from 0.9 to 0.15 for a sample of 20,000 subjects; or (3) assortative mating occurs (spouse correlation of the underlying liability to the disorder), which decreases the SNP heritability but not the power to detect a single locus in the trio design. Some studies use unscreened rather than screened control subjects because these can be easier to collect; we show that the estimated SNP heritability should then be scaled by dividing by (1 - K × u)(2) for disorders with population prevalence K and proportion of unscreened control subjects u. When omitting to scale appropriately, the SNP heritability of, for example, major depressive disorder (K = 0.15) would be underestimated by 28% when none of the control subjects are screened.
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