Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Khatri, Bhuwan; Martín Ibáñez, Javier; Teruel, María; Alarcón Riquelme, Marta Eugenia; PRECISESADS Clinical Consortium; Sjogrens Int Collaborative Clinica; UK Primary Sjogrens Syndrome Regis

doi:10.1038/s41467-022-30773-y

s41467-022-30773-y.pdf (3.018Mb)

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Identificadores

URI: http://hdl.handle.net/10481/76661

DOI: 10.1038/s41467-022-30773-y

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Editorial

Nature

Fecha

2022-07-27

Referencia bibliográfica

Khatri, B... [et al.]. Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells. Nat Commun 13, 4287 (2022). [https://doi.org/10.1038/s41467-022-30773-y]

Patrocinador

United States Department of Health & Human Services National Institutes of Health (NIH) - USA HHSN268200782096C HHSN268201100011I HHSN268201200008I R01AR073855 R01AR065953 R01AR074310 P50AR060804 R01AR050782 R01DE018209 R33AR076803 R21AR079089; NIDCR Sjogren's Syndrome Clinic NIDCR Division of Intramural Research at the National Institutes of Health funds Z01-DE000704; German Research Foundation (DFG) EXC 2155 390874280; Research Council of Norway 240421 316120; Western Norway Regional Health Authority (Helse Vest) 911807 912043; Swedish Research Council for Medicine and Health Swedish Rheumatism Association King Gustav V's 80-year Foundation Swedish Society of Medicine Swedish Cancer Society; Sjogren's Syndrome Foundation Phileona Foundation Stockholm County Council Swedish Research Council; European Commission 2017-000641; Assistance Publique-Hopitaux de Paris (Ministry of Health) P060228; French society of Rheumatology; United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Aging (NIA) RC2 AG036495 RC4 AG039029 United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Dental & Craniofacial Research (NIDCR) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Eye Institute (NEI) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH Office of Research on Women's Health (ORWH) N01-DE-32636 NIDCR through CIDR's NIH contract

Resumen

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1- MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

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