Advertisement

Clinical Research and Public HealthIn-Press PreviewAutoimmunityGeneticsImmunology Open Access | 10.1172/JCI205952

Tissue-specific clustering of genetic correlations across autoimmune diseases in a nationwide sibling study

Daniel Eriksson,1 Ralf Kuja-Halkola,2 Marie E. Holmqvist,3 Henrik Larsson,2 Agnieszka Butwicka,2 Soffia Gudbjörnsdottir,4 Olle Kämpe,3 Sophie Bensing,3 and Jakob Skov3

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Eriksson, D. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Kuja-Halkola, R. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Holmqvist, M. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Larsson, H. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Butwicka, A. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Gudbjörnsdottir, S. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Kämpe, O. in: PubMed | Google Scholar

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Bensing, S. in: PubMed | Google Scholar |

1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

3Department of Medicine, Karolinska Institutet, Stockholm, Sweden

4Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden

Find articles by Skov, J. in: PubMed | Google Scholar

Published August 3, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI205952.
Copyright © 2026, Eriksson et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 3, 2026 - Version history
View PDF
Abstract

Background Autoimmune diseases (ADs) often co-occur within individuals and families, indicating shared genetic risk factors. However, the composition of genetic overlap across autoimmunity is largely unknown. Methods This nationwide study included 6,336,615 individuals born in Sweden between 1932 and 1983, comprising 3,839,400 full-sibling pairs. Based on national heath-registers, 22 ADs were identified from 1969-2013. Aggregation and co-aggregation of ADs among siblings was used to estimate pairwise genetic correlations of ADs under a liability-threshold model. Network analysis and principal component analysis was used to characterize the structure of shared genetic risk across ADs. Results A total of 707,995 individuals (11.2%) were diagnosed with at least one AD. The studied ADs formed a network of significant genetic correlations (mean rg = 0.24, range 0.08-0.84) with clusters of more closely related ADs (rg ≥ 0.3). We found no evidence of a significant universal factor predisposing to autoimmunity. Conclusions This study demonstrates that ADs share substantial cluster-specific genetic overlap that largely aligns with affected tissue types, leading to distinct groupings of connective tissue diseases, gastrointestinal disorders, and endocrinopathies, whereas diseases of the nervous system show limited genetic cohesion. This suggests that shared biological mechanisms may drive coaggregation within disease groups. Clinically, these insights highlight the importance of monitoring patients and their relatives for related autoimmune disorders. Funding The Swedish Society of Medicine, Region Värmland's County Research Council, The Swedish Research Council, the Knut and Alice Wallenberg Foundation, The Regional Agreement on medical training and Clinical research (ALF) between Stockholm County Council and Karolinska Institutet

Graphical Abstract
graphical abstract
Supplemental material

View

Version history
  • Version 1 (August 3, 2026): In-Press Preview
Advertisement
Advertisement