A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy
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A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy. / Athanasiadis, Georgios; Meijsen, Joeri J.; Helenius, Dorte; Schork, Andrew J.; Ingason, Andrés; Thompson, Wesley K.; Geschwind, Daniel H.; Werge, Thomas; Buil, Alfonso.
In: PNAS, Vol. 119, No. 6, e2118688119, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.
PY - 2022
Y1 - 2022
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 h2 = 0.406, 95% CI = [0.403, 0.408]), whereas estimates for cancers were the lowest (average h2 = 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 h2 = 0.406, 95% CI = [0.403, 0.408]), whereas estimates for cancers were the lowest (average h2 = 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.
KW - Denmark
KW - Genetic correlation
KW - Heritability
KW - Human disease
KW - Register data
U2 - 10.1073/pnas.2118688119
DO - 10.1073/pnas.2118688119
M3 - Journal article
C2 - 35131856
AN - SCOPUS:85124317632
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6
M1 - e2118688119
ER -
ID: 300156217