期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：6
DOI：10.1073/pnas.2118688119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The ability to extract multigenerational family relationships from large-scale population cohorts provides a powerful means to understand the heritability of a wide range of diseases and their genetic relationships to each other. By showing how the heritability of broad diagnostic categories changes over time and how said categories are related on the genetic level, our analysis of the Danish genealogy and linked national patient registers illustrates the vast potential of this resource in current biomedical research.
For more than half a century, Denmark has maintained population-wide demographic, health care, and socioeconomic registers that provide detailed information on the interaction between all residents and the extensive national social services system. We leverage this resource to reconstruct the genealogy of the entire nation based on all individuals legally residing in Denmark since 1968. We cross-reference 6,691,426 individuals with nationwide health care registers to estimate heritability and genetic correlations of 10 broad diagnostic categories involving all major organs and systems. Heritability estimates for mental disorders were consistently the highest across demographic cohorts (average
h
2 = 0.406, 95% CI = [0.403, 0.408]), whereas estimates for cancers were the lowest (average
h
2 = 0.130, 95% CI = [0.125, 0.134]). The average genetic correlation of each of the 10 diagnostic categories with the other nine was highest for gastrointestinal conditions (average
r
g
= 0.567, 95% CI = [0.566, 0.567]) and lowest for urogenital conditions (average
r
g
= 0.386, 95% CI = [0.385, 0.388]). Mental, pulmonary, gastrointestinal, and neurological conditions had similar genetic correlation profiles.
