| Title: | Transcriptome-Wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations |
| Journal: | Genes |
| Published: | 8 Jul 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34356065/ |
| DOI: | https://doi.org/10.3390/genes12071049 |
| URL: | https://escholarship.org/uc/item/1t91v1vp |
Publication 5915
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Abstract
BACKGROUND: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Moreover, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed.</p>
METHODS: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including n = 229 African American and n = 381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, n = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (n = 27,955) and Hispanic/Latino (n = 28,324) ancestry participants.</p>
RESULTS: Our results revealed 24 suggestive signals (p < 1 × 10-4) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN.</p>
CONCLUSIONS: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.</p>
12 Keywords
- Black or African American
- Blood Cells
- Cohort Studies
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Hispanic or Latino
- Humans
- Phenotype
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- Transcriptome
- White People
36 Authors
- Jia Wen
- Munan Xie
- Bryce Rowland
- Jonathan D. Rosen
- Quan Sun
- Jiawen Chen
- Amanda L. Tapia
- Huijun Qian
- Madeline H. Kowalski
- Yue Shan
- Kristin L. Young
- Marielisa Graff
- Maria Argos
- Christy L. Avery
- Stephanie A. Bien
- Steve Buyske
- Jie Yin
- Hélène Choquet
- Myriam Fornage
- Chani J. Hodonsky
- Eric Jorgenson
- Charles Kooperberg
- Ruth J. F. Loos
- Yongmei Liu
- Jee-Young Moon
- Kari E. North
- Stephen S. Rich
- Jerome I. Rotter
- Jennifer A. Smith
- Wei Zhao
- Lulu Shang
- Tao Wang
- Xiang Zhou
- Alexander P. Reiner
- Laura M. Raffield
- Yun Li
1 Application
| Application ID | Title |
|---|---|
| 25953 | Transcriptome-wide Association Study of Cardiometabolic Traits in the UK Biobank Cohort |
Enabling scientific discoveries that improve human health