ArticleBMC genomics2020
Ancestry-specific associations identified in genome-wide combined-phenotype study of red blood cell traits emphasize benefits of diversity in genomics.
Article in BMC genomics, 2020. 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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16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
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- Sparse haplotype-based fine-scale local ancestry inference at scale reveals recent selection on immune responses.Nature communications · 2025Article
- Interplay between hereditary and acquired factors determines the neutrophil counts in older individuals.Blood advances · 2023Article
- Eligibility Considerations for Female Whole Blood Donors: Hemoglobin Levels and Iron Status in a Nationally Representative Population.Transfusion medicine reviews · 2023Article
- Single nucleotide variants in microRNA biosynthesis genes in Mexican individuals.Frontiers in genetics · 2023Article
- Pan-African genome demonstrates how population-specific genome graphs improve high-throughput sequencing data analysis.Nature communications · 2022Article
- ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia.Blood · 2022Article
- HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study.Frontiers in endocrinology · 2022Article
- Bayesian model comparison for rare-variant association studies.American journal of human genetics · 2021Article
- The genetic architecture of temperature adaptation is shaped by population ancestry and not by selection regime.Genome biology · 2021Article
- Comparison of adaptive multiple phenotype association tests using summary statistics in genome-wide association studies.Human molecular genetics · 2021Article
- Article
- Genome-Wide Association and Mendelian Randomization Analysis Reveal the Causal Relationship Between White Blood Cell Subtypes and Asthma in Africans.Frontiers in genetics · 2021Article
- A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs.Frontiers in immunology · 2021Article
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Authors and funding
21 authors at 10 institutions in 1 country.
Funding
Abstract
backgroundQuantitative red blood cell (RBC) traits are highly polygenic clinically relevant traits, with approximately 500 reported GWAS loci. The majority of RBC trait GWAS have been performed in European- or East Asian-ancestry populations, despite evidence that rare or ancestry-specific variation contributes substantially to RBC trait heritability. Recently developed combined-phenotype methods which leverage genetic trait correlation to improve statistical power have not yet been applied to these traits. Here we leveraged correlation of seven quantitative RBC traits in performing a combined-phenotype analysis in a multi-ethnic study population.
resultsWe used the adaptive sum of powered scores (aSPU) test to assess combined-phenotype associations between ~ 21 million SNPs and seven RBC traits in a multi-ethnic population (maximum n = 67,885 participants; 24% African American, 30% Hispanic/Latino, and 43% European American; 76% female). Thirty-nine loci in our multi-ethnic population contained at least one significant association signal (p < 5E-9), with lead SNPs at nine loci significantly associated with three or more RBC traits. A majority of the lead SNPs were common (MAF > 5%) across all ancestral populations. Nineteen additional independent association signals were identified at seven known loci (HFE, KIT, HBS1L/MYB, CITED2/FILNC1, ABO, HBA1/2, and PLIN4/5). For example, the HBA1/2 locus contained 14 conditionally independent association signals, 11 of which were previously unreported and are specific to African and Amerindian ancestries. One variant in this region was common in all ancestries, but exhibited a narrower LD block in African Americans than European Americans or Hispanics/Latinos. GTEx eQTL analysis of all independent lead SNPs yielded 31 significant associations in relevant tissues, over half of which were not at the gene immediately proximal to the lead SNP.
conclusionThis work identified seven loci containing multiple independent association signals for RBC traits using a combined-phenotype approach, which may improve discovery in genetically correlated traits. Highly complex genetic architecture at the HBA1/2 locus was only revealed by the inclusion of African Americans and Hispanics/Latinos, underscoring the continued importance of expanding large GWAS to include ancestrally diverse populations.
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