ArticleHuman molecular genetics2021
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.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Meta-analysis ofInternational journal of immunopathology and pharmacologyPooled it
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- From autoimmune inflammation to malignancy: causal genetic evidence for the RA-squamous cell lung cancer axis.Arthritis research & therapy · 2025Article
- Association of MSH2, MSH6, and MLH1 polymorphisms with susceptibility and survival in lung cancer patients.Genes & genomics · 2025Article
- Genome-Wide Association Study of Cognitive Function in Population-Based Cohorts in Japan: The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study.Genes, brain, and behavior · 2025Article
- Nerve growth factor gene polymorphisms may be associated with heroin dependence in women but do not mediate specific personality traits.European archives of psychiatry and clinical neuroscience · 2025Article
- Characterizing the polygenic architecture of complex traits in populations of East Asian and European descent.Human genomics · 2023Article
- Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program.Human genomics · 2023Article
- Sex differences in the polygenic architecture of hearing problems in adults.Genome medicine · 2023Article
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7 authors.
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Abstract
To investigate cross-ancestry genetics of complex traits, we conducted a phenome-wide analysis of loci with heterogeneous effects across African, Admixed-American, Central/South Asian, East Asian, European and Middle Eastern participants of the UK Biobank (N = 441 331). Testing 843 phenotypes, we identified 82 independent genomic regions mapping variants showing genome-wide significant (GWS) associations (P < 5 × 10-8) in the trans-ancestry meta-analysis and GWS heterogeneity among the ancestry-specific effects. These included (i) loci with GWS association in one ancestry and concordant but heterogeneous effects among the other ancestries and (ii) loci with a GWS association in one ancestry group and an experiment-wide significant discordant effect (P < 6.1 × 10-4) in at least another ancestry. Since the trans-ancestry GWS associations were mostly driven by the European ancestry sample size, we investigated the differences of the allele frequency (ΔAF) and linkage disequilibrium regulome tagging (ΔLD) between European populations and the other ancestries. Within loci with concordant effects, the degree of heterogeneity was associated with European-Middle Eastern ΔAF (P = 9.04 × 10-6) and ΔLD of European populations with respect to African, Admixed-American and Central/South Asian groups (P = 8.21 × 10-4, P = 7.17 × 10-4 and P = 2.16 × 10-3, respectively). Within loci with discordant effects, ΔAF and ΔLD of European populations with respect to African and Central/South Asian ancestries were associated with the degree of heterogeneity (ΔAF: P = 7.69 × 10-3 and P = 5.31 × 10-3, ΔLD: P = 0.016 and P = 2.65 × 10-4, respectively). Considering the traits associated with cross-ancestry heterogeneous loci, we observed enrichments for blood biomarkers (P = 5.7 × 10-35) and physical appearance (P = 1.38 × 10-4). This suggests that these specific phenotypic classes may present considerable cross-ancestry heterogeneity owing to large allele frequency and LD variation among worldwide populations.
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