Evidence map›Paper›PMID 31315583›Full record

SynthesisBMC genetics2019

Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.

Frida Lona-Durazo, Natalia Hernandez-Pacheco, Shaohua Fan, Tongwu Zhang, Jiyeon Choi, Michael A Kovacs, Stacie K Loftus, Phuong Le, Melissa Edwards, Cesar A Fortes-Lima and 16 more

Open access · diamondAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% of its field
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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Beyond the Classics: The Synergy of AI and Genomics Reveals an Expanded Repertoire of Pigmentation Genes.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2026
    Review
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  8. Interpreting SNP heritability in admixed populations.bioRxiv : the preprint server for biology · 2025
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  20. Advances in integrative African genomics.Trends in genetics : TIG · 2022
    Review
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

26 authors at 11 institutions in 8 countries.

Frida Lona-DurazoDepartment of Anthropology, University of Toronto at Mississauga, Health Sciences Complex, room 352, Mississauga, Ontario, L5L 1C6, Canada.
Natalia Hernandez-PachecoResearch Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Shaohua FanDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Tongwu ZhangLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Jiyeon ChoiLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Michael A KovacsLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Stacie K LoftusGenetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, USA.
Phuong LeDepartment of Anthropology, University of Toronto at Mississauga, Health Sciences Complex, room 352, Mississauga, Ontario, L5L 1C6, Canada.
Melissa EdwardsDepartment of Anthropology, University of Toronto at Mississauga, Health Sciences Complex, room 352, Mississauga, Ontario, L5L 1C6, Canada.
Cesar A Fortes-LimaEvolutionary Anthropology Team, Laboratory Eco-Anthropology and Ethno-Biology UMR7206, CNRS-MNHN-University Paris Diderot, Musée de l'Homme, Paris, France.
Celeste EngDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Scott HuntsmanDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Donglei HuDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Enrique Javier Gómez-CabezasCentre for Sociological and Psychological Research, Havana, Cuba.
Lilia Caridad Marín-PadrónNational Centre of Medical Genetics, Medical University of Havana, La Habana, Cuba.
Jonas GrauholmDepartment for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Ole MorsTranslational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Esteban G BurchardDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Heather L NortonDepartment of Anthropology, University of Cincinnati, Cincinnati, USA.
William J PavanGenetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, USA.
Kevin M BrownLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
Sarah TishkoffDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Maria Pino-YanesGenomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Tenerife, Spain.
Sandra BelezaDepartment of Genetics and Genome Biology, College of Life Sciences, University of Leicester, Leicester, UK.
Beatriz Marcheco-TeruelNational Centre of Medical Genetics, Medical University of Havana, La Habana, Cuba.
Esteban J ParraDepartment of Anthropology, University of Toronto at Mississauga, Health Sciences Complex, room 352, Mississauga, Ontario, L5L 1C6, Canada. esteban.parra@utoronto.ca.ORCID 0000-0002-2057-8577
National Institutes of Health · USUniversity of California, San Francisco · USUniversity of Toronto · CAUniversidad de La Laguna · ESUniversity of Havana · CUUniversity of Pennsylvania · USAarhus University · DKStatens Serum Institut · DKUniversity of Cincinnati · USUniversity of Leicester · GBUppsala University · SE

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
The Airway Functional Genomics of Bronchodilator Drug Response in Minority Children with AsthmaR01HL117004 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, SEIBOLD, MAX A · 2013 to 2022
$9.3M
Social Interventions to address disparities In young adult tobacco useP60MD006902 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIBBINS-DOMINGO, KIRSTEN · 2012 to 2016
$6.4M
Gene-environments and Admixture in Latino Asthmatics (GALA 2)R01ES015794 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ · 2008 to 2012
$5.4M
Genes, air pollution, and asthma severity in minority childrenR01MD010443 · NIMHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SEIBOLD, MAX A, ZIV, ELAD · 2016 to 2020
$3.8M
Genetic Control of Airway Epithelium Gene Expression in Childhood AsthmaticsR01HL128439 · NHLBI · NATIONAL JEWISH HEALTH · PI SEIBOLD, MAX A · 2015 to 2019
$3.1M
Integrative Genomics of Body Size and Metabolism in Ethnically Diverse AfricansR01GM113657 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI TISHKOFF, SARAH ANNE · 2015 to 2019
$2.8M
Integrative Genomic Analyses of Human Evolution and Adaptation in AfricaR35GM134957 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI TISHKOFF, SARAH ANNE · 2020 to 2024
$2.7M
Integrative nutrigenomic and metabolomic analyses of Africans with variable dietsR01DK104339 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI TISHKOFF, SARAH ANNE · 2015 to 2018
$1.4M
Gene-Environment Analyses of Early Life Exposures and Asthma in Ethnically Diverse ChildrenR21ES024844 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURCHARD, ESTEBAN GONZALEZ, GAUDERMAN, WILLIAM JAMES · 2015 to 2017
$509k
Medical Research Council MR/M01987X/1NHLBI NIH HHS R01 HL117004NHLBI NIH HHS R01 HL128439NIDDK NIH HHS R01 DK104339NIEHS NIH HHS P30 ES013508NIEHS NIH HHS R01 ES015794NIEHS NIH HHS R21 ES024844NIGMS NIH HHS R01 GM113657NIGMS NIH HHS R35 GM134957NIMHD NIH HHS P60 MD006902NIMHD NIH HHS R01 MD010443
6 · The paper itself

Abstract

backgroundAssociation studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations.

resultsWe present a GWAS of skin pigmentation in an admixed sample from Cuba (N = 762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N = 2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response.

conclusionsOur meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.

Indexed as

Genetics, PopulationGenome-Wide Association StudyAllelesGenotypeHumansLinkage DisequilibriumPolymorphism, Single NucleotideQuantitative Trait LociSkin PigmentationAdmixed populationsComplex traitGene expressionGenome-wide association studyHaplotypeMeta-analysisSkin pigmentation

Identifiers

PMID31315583
PMCPMC6637524
OpenAlexW2962374818

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.