ArticleGenomics2021
Characterizing the effect of background selection on the polygenicity of brain-related traits.
Article in Genomics, 2021. 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.
- The impact of assortative mating, participation bias and socioeconomic status on the polygenic risk of behavioural and psychiatric traits.Nature human behaviour · 2024Pooled it
- Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records.Molecular psychiatry · 2022Pooled it
- Genomic interplay between deployment exposures and Gulf War illness in Million Veteran Program participants.Human genomics · 2026Article
- Understanding the Emergence of Schizophrenia in the Light of Human Evolution: New Perspectives in Genetics.Genes, brain, and behavior · 2025Review
- Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.Nature genetics · 2024Article
- Enrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders.Human genetics · 2023Article
- Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent.Human genomics · 2023Article
- Examining the shared etiology of psychopathology with genome-wide association studies.Physiological reviews · 2023Review
- Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data.Molecular psychiatry · 2023Article
- Sex-Specific Genetic and Transcriptomic Liability to Neuroticism.Biological psychiatry · 2023Article
- Denisovan and Neanderthal archaic introgression differentially impacted the genetics of complex traits in modern populations.BMC biology · 2022Article
- Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective.Evolutionary human sciences · 2022Review
- Genetics of substance use disorders in the era of big data.Nature reviews. Genetics · 2021Review
- Posttraumatic stress disorder: from gene discovery to disease biology.Psychological medicine · 2021Review
- Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank.Human molecular genetics · 2021Article
- Integration of evidence across human and model organism studies: A meeting report.Genes, brain, and behavior · 2021Review
Corrections and comments
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Authors and funding
7 authors.
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Abstract
backgroundGenome-wide association studies (GWAS) have demonstrated that psychopathology phenotypes are affected by many risk alleles with small effect (polygenicity). It is unclear how ubiquitously evolutionary pressures influence the genetic architecture of these traits.
methodsWe partitioned SNP heritability to assess the contribution of background (BGS) and positive selection, Neanderthal local ancestry, functional significance, and genotype networks in 75 brain-related traits (8411 ≤ N ≤ 1,131,181, mean N = 205,289). We applied binary annotations by dichotomizing each measure based on top 2%, 1%, and 0.5% of all scores genome-wide. Effect size distribution features were calculated using GENESIS. We tested the relationship between effect size distribution descriptive statistics and natural selection. In a subset of traits, we explore the inclusion of diagnostic heterogeneity (e.g., number of diagnostic combinations and total symptoms) in the tested relationship.
resultsSNP-heritability was enriched (false discovery rate q < 0.05) for loci with elevated BGS (7 phenotypes) and in genic (34 phenotypes) and loss-of-function (LoF)-intolerant regions (67 phenotypes). These effects were strongest in GWAS of schizophrenia (1.90-fold BGS, 1.16-fold genic, and 1.92-fold LoF), educational attainment (1.86-fold BGS, 1.12-fold genic, and 1.79-fold LoF), and cognitive performance (2.29-fold BGS, 1.12-fold genic, and 1.79-fold LoF). BGS (top 2%) significantly predicted effect size variance for trait-associated loci (σ
conclusionsBrain-related phenotypes with larger variance in risk locus effect sizes are associated with loci under BGS. We show exploratory results suggesting that diagnostic complexity may also contribute to the increased polygenicity of psychiatric disorders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.