TY - JOUR
T1 - Declining autozygosity over time
T2 - An exploration in over 1 million individuals from three diverse cohorts
AU - Colbert, Sarah M.C.
AU - Wendt, Frank R.
AU - Pathak, Gita A.
AU - Helmer, Drew A.
AU - Hauser, Elizabeth R.
AU - Keller, Matthew C.
AU - Polimanti, Renato
AU - Johnson, Emma C.
N1 - Publisher Copyright:
© 2023 American Society of Human Genetics
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - F
KW - autozygosity
KW - panmixia
KW - runs of homozygosity
UR - http://www.scopus.com/inward/record.url?scp=85160020337&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2023.04.007
DO - 10.1016/j.ajhg.2023.04.007
M3 - Article
C2 - 37178685
AN - SCOPUS:85160020337
SN - 0002-9297
VL - 110
SP - 1008
EP - 1014
JO - American journal of human genetics
JF - American journal of human genetics
IS - 6
ER -