Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
Bhuwan KhatriKandice L TessneerAstrid RasmussenFarhang AghakhanianTove Ragna RekstenAdam AdlerIlias AlevizosJuan-Manuel AnayaLara A AqrawiEva BaecklundJohan G BrunSara Magnusson BucherMaija-Leena ElorantaFiona EngelkeHelena Forsblad-d'EliaStuart B GlennDaniel HammenforsJuliana Imgenberg-KreuzJanicke Liaaen JensenSvein Joar Auglænd JohnsenMalin V JonssonMarika KvarnströmJennifer A KellyHe LiThomas MandlJavier MartínGaetane NocturneKatrine Brække NorheimØyvind PalmKathrine SkarsteinAnna M StolarczykKimberly E TaylorMaria TeruelElke TheanderSwamy VenuturupalliDaniel J WallaceKiely M GrundahlKimberly S HefnerLida RadfarDavid M LewisDonald U StoneC Erick KaufmanMichael T BrennanJoel M GuthridgeJudith A JamesR Hal ScofieldPatrick M GaffneyLindsey A CriswellRoland JonssonPer ErikssonSimon J BowmanRoald OmdalLars RönnblomBlake M WarnerMaureen RischmuellerTorsten WitteA Darise FarrisXavier MarietteMarta Eugenia Alarcón-Riquelmenull nullCaroline H Shiboskinull nullMarie Wahren-HerleniusWan-Fai Ngnull nullKathy L SivilsIndra AdriantoGunnel NordmarkChristopher J LessardPublished in: Nature communications (2022)
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.
Keyphrases
- genome wide association study
- genome wide
- dna methylation
- copy number
- disease activity
- induced apoptosis
- cell proliferation
- long non coding rna
- multiple sclerosis
- rheumatoid arthritis
- gene expression
- transcription factor
- advanced non small cell lung cancer
- long noncoding rna
- machine learning
- oxidative stress
- deep learning
- big data
- signaling pathway
- drug induced
- tyrosine kinase