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Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program.

Publication ,  Journal Article
Wendt, FR; Pathak, GA; Vahey, J; Qin, X; Koller, D; Cabrera-Mendoza, B; Haeny, A; Harrington, KM; Rajeevan, N; Duong, LM; Levey, DF; Aslan, M ...
Published in: Hum Genomics
June 2, 2023

BACKGROUND: The Million Veteran Program (MVP) participants represent 100 years of US history, including significant social and demographic changes over time. Our study assessed two aspects of the MVP: (i) longitudinal changes in population diversity and (ii) how these changes can be accounted for in genome-wide association studies (GWAS). To investigate these aspects, we divided MVP participants into five birth cohorts (N-range = 123,888 [born from 1943 to 1947] to 136,699 [born from 1948 to 1953]). RESULTS: Ancestry groups were defined by (i) HARE (harmonized ancestry and race/ethnicity) and (ii) a random-forest clustering approach using the 1000 Genomes Project and the Human Genome Diversity Project (1kGP + HGDP) reference panels (77 world populations representing six continental groups). In these groups, we performed GWASs of height, a trait potentially affected by population stratification. Birth cohorts demonstrate important trends in ancestry diversity over time. More recent HARE-assigned Europeans, Africans, and Hispanics had lower European ancestry proportions than older birth cohorts (0.010 < Cohen's d < 0.259, p < 7.80 × 10-4). Conversely, HARE-assigned East Asians showed an increase in European ancestry proportion over time. In GWAS of height using HARE assignments, genomic inflation due to population stratification was prevalent across all birth cohorts (linkage disequilibrium score regression intercept = 1.08 ± 0.042). The 1kGP + HGDP-based ancestry assignment significantly reduced the population stratification (mean intercept reduction = 0.045 ± 0.007, p < 0.05) confounding in the GWAS statistics. CONCLUSIONS: This study provides a characterization of ancestry diversity of the MVP cohort over time and compares two strategies to infer genetically defined ancestry groups by assessing differences in controlling population stratification in genome-wide association studies.

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Published In

Hum Genomics

DOI

EISSN

1479-7364

Publication Date

June 2, 2023

Volume

17

Issue

1

Start / End Page

46

Location

England

Related Subject Headings

  • Veterans
  • Racial Groups
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Ethnicity
  • 3105 Genetics
  • 3101 Biochemistry and cell biology
 

Citation

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Wendt, F. R., Pathak, G. A., Vahey, J., Qin, X., Koller, D., Cabrera-Mendoza, B., … Department of Veteran Affairs Cooperative Study Program (#2006), . (2023). Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. Hum Genomics, 17(1), 46. https://doi.org/10.1186/s40246-023-00487-3
Wendt, Frank R., Gita A. Pathak, Jacqueline Vahey, Xuejun Qin, Dora Koller, Brenda Cabrera-Mendoza, Angela Haeny, et al. “Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program.Hum Genomics 17, no. 1 (June 2, 2023): 46. https://doi.org/10.1186/s40246-023-00487-3.
Wendt FR, Pathak GA, Vahey J, Qin X, Koller D, Cabrera-Mendoza B, et al. Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. Hum Genomics. 2023 Jun 2;17(1):46.
Wendt, Frank R., et al. “Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program.Hum Genomics, vol. 17, no. 1, June 2023, p. 46. Pubmed, doi:10.1186/s40246-023-00487-3.
Wendt FR, Pathak GA, Vahey J, Qin X, Koller D, Cabrera-Mendoza B, Haeny A, Harrington KM, Rajeevan N, Duong LM, Levey DF, De Angelis F, De Lillo A, Bigdeli TB, Pyarajan S, VA Million Veteran Program, Gaziano JM, Gelernter J, Aslan M, Provenzale D, Helmer DA, Hauser ER, Polimanti R, Department of Veteran Affairs Cooperative Study Program (#2006). Modeling the longitudinal changes of ancestry diversity in the Million Veteran Program. Hum Genomics. 2023 Jun 2;17(1):46.
Journal cover image

Published In

Hum Genomics

DOI

EISSN

1479-7364

Publication Date

June 2, 2023

Volume

17

Issue

1

Start / End Page

46

Location

England

Related Subject Headings

  • Veterans
  • Racial Groups
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetics & Heredity
  • Ethnicity
  • 3105 Genetics
  • 3101 Biochemistry and cell biology