Back to Search
Start Over
Whole-genome sequencing in diverse subjects identifies genetic correlates of leukocyte traits: The NHLBI TOPMed program.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2021 Oct 07; Vol. 108 (10), pp. 1836-1851. Date of Electronic Publication: 2021 Sep 27. - Publication Year :
- 2021
-
Abstract
- Many common and rare variants associated with hematologic traits have been discovered through imputation on large-scale reference panels. However, the majority of genome-wide association studies (GWASs) have been conducted in Europeans, and determining causal variants has proved challenging. We performed a GWAS of total leukocyte, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts generated from 109,563,748 variants in the autosomes and the X chromosome in the Trans-Omics for Precision Medicine (TOPMed) program, which included data from 61,802 individuals of diverse ancestry. We discovered and replicated 7 leukocyte trait associations, including (1) the association between a chromosome X, pseudo-autosomal region (PAR), noncoding variant located between cytokine receptor genes (CSF2RA and CLRF2) and lower eosinophil count; and (2) associations between single variants found predominantly among African Americans at the S1PR3 (9q22.1) and HBB (11p15.4) loci and monocyte and lymphocyte counts, respectively. We further provide evidence indicating that the newly discovered eosinophil-lowering chromosome X PAR variant might be associated with reduced susceptibility to common allergic diseases such as atopic dermatitis and asthma. Additionally, we found a burden of very rare FLT3 (13q12.2) variants associated with monocyte counts. Together, these results emphasize the utility of whole-genome sequencing in diverse samples in identifying associations missed by European-ancestry-driven GWASs.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 American Society of Human Genetics. All rights reserved.)
- Subjects :
- Asthma genetics
Asthma metabolism
Asthma pathology
Dermatitis, Atopic genetics
Dermatitis, Atopic metabolism
Dermatitis, Atopic pathology
Genetic Predisposition to Disease
Genome, Human
Genome-Wide Association Study
Humans
National Heart, Lung, and Blood Institute (U.S.)
Phenotype
Prognosis
Proteome analysis
Proteome metabolism
Pulmonary Disease, Chronic Obstructive genetics
Pulmonary Disease, Chronic Obstructive metabolism
Pulmonary Disease, Chronic Obstructive pathology
United Kingdom epidemiology
United States epidemiology
Whole Genome Sequencing
Asthma epidemiology
Biomarkers metabolism
Dermatitis, Atopic epidemiology
Leukocytes pathology
Polymorphism, Single Nucleotide
Pulmonary Disease, Chronic Obstructive epidemiology
Quantitative Trait Loci
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 108
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 34582791
- Full Text :
- https://doi.org/10.1016/j.ajhg.2021.08.007