Transcriptome-Wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations

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Citation

Wen, Jia; Xie, Munan; Rowland, Bryce; Rosen, Jonathan D.; Sun, Quan; Chen, Jiawen; Tapia, Amanda L.; Qian, Huijun; Kowalski, Madeline H.; & Shan, Yue, et al. (2021). Transcriptome-Wide Association Study of Blood Cell Traits in African Ancestry and Hispanic/Latino Populations. Genes (Basel), 12(7), 1049. PMCID: PMC8307403

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.
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.
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.
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.

URL

http://dx.doi.org/10.3390/genes12071049

Reference Type

Journal Article

Year Published

2021

Journal Title

Genes (Basel)

Author(s)

Wen, Jia
Xie, Munan
Rowland, Bryce
Rosen, Jonathan D.
Sun, Quan
Chen, Jiawen
Tapia, Amanda L.
Qian, Huijun
Kowalski, Madeline H.
Shan, Yue
Young, Kristin L.
Graff, Mariaelisa
Argos, Maria
Avery, Christy L.
Bien, Stephanie A.
Buyske, Steven G.
Yin, Jie
Choquet, Helene
Fornage, Myriam
Hodonsky, Chani J.
Jorgenson, Eric
Kooperberg, Charles L.
Loos, Ruth J. F.
Liu, YongMei
Moon, Jee-Young
North, Kari E.
Rich, Stephen S.
Rotter, Jerome I.
Smith, Jennifer A.
Zhao, Wei
Shang, Lulu
Wang, Tao
Zhou, Xiang
Reiner, Alexander P.
Raffield, Laura M.
Li, Yun

Article Type

Regular

PMCID

PMC8307403

Data Set/Study

Multi-Ethnic Study of Atherosclerosis (MESA)
Depression Genes and Networks

Continent/Country

United States of America

State

Nonspecific

Race/Ethnicity

African Ancestry
European Ancestry
Hispanic Ancestry

ORCiD

Graff - 0000-0001-6380-1735
Avery - 0000-0002-1044-8162