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Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts.

Publication ,  Journal Article
Colbert, SMC; Wendt, FR; Pathak, GA; Helmer, DA; Hauser, ER; Keller, MC; Polimanti, R; Johnson, EC
Published in: Am J Hum Genet
June 1, 2023

Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = -0.029, SE = 0.009, p = 6.03e-4). On the basis of our estimates, we would predict FROH to decline 0.29% for every 20-year increase in birth year. We determined that a model including an ancestry-by-country interaction term fit the data best, indicating that ancestry differences in this trend differ by country. We found further evidence to suggest a difference between the US and UK cohorts by meta-analyzing within country, observing a significant negative estimate in the US cohorts (meta-analyzed slope = -0.058, SE = 0.015, p = 1.50e-4) but a non-significant estimate in the UK (meta-analyzed slope = -0.001, SE = 0.008, p = 0.945). The association between autozygosity and birth year was substantially attenuated when accounting for educational attainment and income (meta-analyzed slope = -0.011, SE = 0.008, p = 0.167), suggesting they may partially account for decreasing autozygosity over time. Overall, we demonstrate decreasing autozygosity over time in a large, modern sample and speculate that this trend can be attributed to increases in urbanization and panmixia and differences in sociodemographic processes lead to country-specific differences in the rate of decline.

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Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

June 1, 2023

Volume

110

Issue

6

Start / End Page

1008 / 1014

Location

United States

Related Subject Headings

  • Population Health
  • Polymorphism, Single Nucleotide
  • Humans
  • Homozygote
  • Genetics & Heredity
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Colbert, S. M. C., Wendt, F. R., Pathak, G. A., Helmer, D. A., Hauser, E. R., Keller, M. C., … Johnson, E. C. (2023). Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts. Am J Hum Genet, 110(6), 1008–1014. https://doi.org/10.1016/j.ajhg.2023.04.007
Colbert, Sarah M. C., Frank R. Wendt, Gita A. Pathak, Drew A. Helmer, Elizabeth R. Hauser, Matthew C. Keller, Renato Polimanti, and Emma C. Johnson. “Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts.Am J Hum Genet 110, no. 6 (June 1, 2023): 1008–14. https://doi.org/10.1016/j.ajhg.2023.04.007.
Colbert SMC, Wendt FR, Pathak GA, Helmer DA, Hauser ER, Keller MC, et al. Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts. Am J Hum Genet. 2023 Jun 1;110(6):1008–14.
Colbert, Sarah M. C., et al. “Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts.Am J Hum Genet, vol. 110, no. 6, June 2023, pp. 1008–14. Pubmed, doi:10.1016/j.ajhg.2023.04.007.
Colbert SMC, Wendt FR, Pathak GA, Helmer DA, Hauser ER, Keller MC, Polimanti R, Johnson EC. Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts. Am J Hum Genet. 2023 Jun 1;110(6):1008–1014.
Journal cover image

Published In

Am J Hum Genet

DOI

EISSN

1537-6605

Publication Date

June 1, 2023

Volume

110

Issue

6

Start / End Page

1008 / 1014

Location

United States

Related Subject Headings

  • Population Health
  • Polymorphism, Single Nucleotide
  • Humans
  • Homozygote
  • Genetics & Heredity
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences