Evidence map›Paper›PMID 33890984›Full record

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.

Antonella De Lillo, Salvatore D'Antona, Gita A Pathak, Frank R Wendt, Flavio De Angelis, Maria Fuciarelli, Renato Polimanti

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  2. Meta-analysis ofInternational journal of immunopathology and pharmacology
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Antonella De LilloDepartment of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.
Salvatore D'AntonaDepartment of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
Gita A PathakDepartment of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.
Frank R WendtDepartment of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.
Flavio De AngelisDepartment of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.
Maria FuciarelliDepartment of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
Renato PolimantiDepartment of Psychiatry, Yale University School of Medicine, West Haven, CT 06516, USA.

Funding

Genome-wide Investigation of the Interplay Between Age-Related Hearing Loss and Smoking BehaviorsR21DC018098 · NIDCD · YALE UNIVERSITY · PI POLIMANTI, RENATO · 2019 to 2021
$440k
Investigating the Systems Genetics of the Patterns of Polysubstance Abuse and AddictionR21DA047527 · NIDA · YALE UNIVERSITY · PI POLIMANTI, RENATO · 2019 to 2020
$369k
Decoding the Sex-Specific Biological Mechanisms of Psychiatric Disorders Using Genome-Wide AnalysesF32MH122058 · NIMH · YALE UNIVERSITY · PI WENDT, FRANK · 2020 to 2021
$118k
NIDA NIH HHS R21 DA047527NIDCD NIH HHS R21 DC018098NIMH NIH HHS F32 MH122058
6 · The paper itself

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.

Indexed as

AllelesBiological Specimen BanksDatabases, GeneticExomeGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLinkage DisequilibriumMultifactorial InheritancePhenotypePolymorphism, Single NucleotidePrognosisRacial GroupsRisk Factors

Identifiers

PMID33890984
PMCPMC8283210

What Socratic holds

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Registered trials

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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.