TY - JOUR

T1 - A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy

AU - Athanasiadis, Georgios

AU - Meijsen, Joeri J

AU - Helenius, Dorte

AU - Schork, Andrew J

AU - Ingason, Andrés

AU - Thompson, Wesley K

AU - Geschwind, Daniel H

AU - Werge, Thomas

AU - Buil, Alfonso

N1 - Copyright © 2022 the Author(s). Published by PNAS.

PY - 2022/2/8

Y1 - 2022/2/8

N2 - 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 rg = 0.567, 95% CI = [0.566, 0.567]) and lowest for urogenital conditions (average rg = 0.386, 95% CI = [0.385, 0.388]). Mental, pulmonary, gastrointestinal, and neurological conditions had similar genetic correlation profiles.

AB - 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 rg = 0.567, 95% CI = [0.566, 0.567]) and lowest for urogenital conditions (average rg = 0.386, 95% CI = [0.385, 0.388]). Mental, pulmonary, gastrointestinal, and neurological conditions had similar genetic correlation profiles.

UR - http://www.scopus.com/inward/record.url?scp=85124317632&partnerID=8YFLogxK

U2 - 10.1073/pnas.2118688119

DO - 10.1073/pnas.2118688119

M3 - Journal article

C2 - 35131856

VL - 119

JO - National Academy of Sciences. Proceedings

JF - National Academy of Sciences. Proceedings

SN - 0027-8424

IS - 6

M1 - e2118688119

ER -