SEARCHCOHORTepidemiology, gastroenterology

cohort·epidemiology, gastroenterology, immunology, endocrinology, public health·PMC10900254

Phenome-wide Mendelian randomization analysis reveals multiple health comorbidities of coeliac disease

eBioMedicine · 9 authors, 8 centres

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A reduced risk for prostate diseases was also observed.

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A reduced risk for prostate diseases was also observed. A secondary analysis removing MHC region SNPs attenuated associations for type 1 diabetes and non-Hodgkin's lymphoma, suggesting shared genetic aetiology. The findings support the need for comorbidity monitoring in individuals with CeD.

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cohort

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epidemiology

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ORIGINAL PAPER

PMC10900254

Phenome-wide Mendelian randomization analysis reveals multiple health comorbidities of coeliac disease

eBioMedicine

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ABSTRACT

Summary Background Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD. Methods Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium ( R 2 <0.001) were selected from a genome-wide association study including 12,041 CeD cases as the instrumental variables. We first constructed a polygenic risk score for CeD and estimated its associations with 1060 unique clinical outcomes in the UK Biobank study (N = 385,917). We then used two-sample MR analysis to replicate the identified associations using data from the FinnGen study (N = 377,277). We performed a secondary analysis using a genetic instrument without extended MHC gene SNPs. Findings Genetic liability to CeD was associated with 68 clinical outcomes in the UK Biobank, and 38 of the associations were replicated in the FinnGen study. Genetic liability to CeD was associated with a higher risk of several autoimmune diseases (type 1 diabetes and its complications, Graves' disease, Sjögren syndrome, chronic hepatitis, systemic and cutaneous lupus erythematosus, and sarcoidosis), non-Hodgkin's lymphoma, and osteoporosis and a lower risk of prostate diseases. The associations for type 1 diabetes and non-Hodgkin's lymphoma attenuated when excluding SNPs in the MHC region, indicating shared genetic aetiology. Interpretation This study uncovers multiple clinical outcomes associated with genetic liability to CeD, which suggests the necessity of comorbidity monitoring among this population. Funding This project was funded by Karolinska Institutet and the Swedish Research Council. Keywords: Celiac disease, Coeliac disease, Comorbidities, Health effect, Mendelian randomization

CITATION EXPORT

Shuai Yuan, Fangyuan Jiang, Jie Chen et al.. Phenome-wide Mendelian randomization analysis reveals multiple health comorbidities of coeliac disease. eBioMedicine. (2024). https://doi.org/10.1016/j.ebiom.2024.105033

AUTHORS

9 · 8 CENTRES

Shuai Yuan, Fangyuan Jiang, Jie Chen, Benjamin Lebwohl, Peter HR Green, Daniel Leffler, Susanna C Larsson, Xue Li, Jonas F Ludvigsson

aSchool of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
bUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
cDepartment of Medicine, Celiac Disease Center at Columbia University Medical Center, New York, NY, USA
dDepartments of Medicine and Surgical Pathology, Columbia University College of Physicians and Surgeons, New York, NY, USA
eThe Celiac Center at Beth Israel Deaconess Medical Center, Harvard Medical School, USA
fUnit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
gDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
hDepartment of Pediatrics, Orebro University Hospital, Orebro, Sweden