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

Georgios Athanasiadis; Joeri J Meijsen; Dorte Helenius; Andrew J Schork; Andrés Ingason; Wesley K Thompson; Daniel H Geschwind; Thomas Werge; Alfonso Buil

doi:10.1073/pnas.2118688119

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

Proc Natl Acad Sci U S A. 2022 Feb 8;119(6):e2118688119. doi: 10.1073/pnas.2118688119.

Authors

Georgios Athanasiadis^{1

2

3}, Joeri J Meijsen^{4

2}, Dorte Helenius^{4

2}, Andrew J Schork^{4

2

5}, Andrés Ingason^{4

2

6}, Wesley K Thompson^{4

2

7}, Daniel H Geschwind^{8

9

10}, Thomas Werge^{1

2

6

11}, Alfonso Buil^{1

2}

Affiliations

¹ Institute of Biological Psychiatry, Mental Health Services Capital Region of Denmark, Roskilde 4000, Denmark; georgios.athanasiadis@regionh.dk alfonso.buil.demur@regionh.dk thomas.werge@regionh.dk.
² Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus 8210, Denmark.
³ Department of Evolutionary Biology, Ecology and Environmental Sciences, University of Barcelona, Barcelona 08028, Spain.
⁴ Institute of Biological Psychiatry, Mental Health Services Capital Region of Denmark, Roskilde 4000, Denmark.
⁵ Neurogenomics Division, The Translational Genomics Institute, Phoenix, AZ 85004.
⁶ Lundbeck Foundation GeoGenetics Centre, Natural History Museum of Denmark, University of Copenhagen, Copenhagen 1350, Denmark.
⁷ Population Neuroscience and Genetics Lab, University of California San Diego, La Jolla, CA 92093.
⁸ Neurogenetics Program, Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
⁹ Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
¹⁰ Department of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, CA 90095.
¹¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.

Abstract

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 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.

Keywords: Denmark; genetic correlation; heritability; human disease; register data.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Denmark
Genetic Diseases, Inborn / diagnosis*
Genetic Diseases, Inborn / genetics*
Genetic Predisposition to Disease / genetics*
Health Services Research / methods
Humans
Mental Disorders / diagnosis
Mental Disorders / genetics