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

PRECISESADS Clinical Consortium; Sjögren’s International Collaborative Clinical Alliance (SICCA); UK primary Sjögren's Syndrome Registry

doi:10.1038/s41467-022-30773-y

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

PRECISESADS Clinical Consortium
, Sjögren’s International Collaborative Clinical Alliance (SICCA)
, UK primary Sjögren's Syndrome Registry

Oklahoma Medical Research Foundation
University of Bergen
National Institutes of Health
Universidad del Rosario
University of Oslo
Kristiania University College
Uppsala University
Örebro University
Hannover Medical School
University of Gothenburg
Stavanger University Hospital
Karolinska Institutet
Stockholm County Council
Johnson & Johnson
Lund University
Consejo Superior de Investigaciones Científicas (CSIC)
Université Paris-Saclay
University of California at San Francisco
University of Granada
Medical Affairs
Cedars-Sinai Medical Center
University of California at Los Angeles
Hefner Eye Care and Optical Center
University of Oklahoma
Carolinas Medical Center
Wake Forest University
Department of Veterans Affairs
Newcastle University
Newcastle upon Tyne Hospitals NHS Foundation Trust
Linköping University
University Hospitals Birmingham NHS Foundation Trust
University of Birmingham
Milton Keynes University Hospital NHS Foundation Trust
Queen Elizabeth Hospital Australia
University of Adelaide
Henry Ford Health System

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	4287
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30773-y
Publication status	Published - Dec 2022
Externally published	Yes

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10.1038/s41467-022-30773-y

Cite this

@article{6d1d218759584b02999ceefd49273f1f,

title = "Genome-wide association study identifies Sj{\"o}gren{\textquoteright}s risk loci with functional implications in immune and glandular cells",

abstract = "Sj{\"o}gren{\textquoteright}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 Sj{\"o}gren{\textquoteright}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.",

author = "\{PRECISESADS Clinical Consortium\} and \{Sj{\"o}gren{\textquoteright}s International Collaborative Clinical Alliance (SICCA)\} and \{UK primary Sj{\"o}gren's Syndrome Registry\} and Bhuwan Khatri and Tessneer, \{Kandice L.\} and Astrid Rasmussen and Farhang Aghakhanian and Reksten, \{Tove Ragna\} and Adam Adler and Ilias Alevizos and Anaya, \{Juan Manuel\} and Aqrawi, \{Lara A.\} and Eva Baecklund and Brun, \{Johan G.\} and Bucher, \{Sara Magnusson\} and Eloranta, \{Maija Leena\} and Fiona Engelke and Helena Forsblad-d{\textquoteright}Elia and Glenn, \{Stuart B.\} and Daniel Hammenfors and Juliana Imgenberg-Kreuz and Jensen, \{Janicke Liaaen\} and Johnsen, \{Svein Joar Augl{\ae}nd\} and Jonsson, \{Malin V.\} and Marika Kvarnstr{\"o}m and Kelly, \{Jennifer A.\} and He Li and Thomas Mandl and Javier Mart{\'i}n and Ga{\'e}tane Nocturne and Norheim, \{Katrine Br{\ae}kke\} and {\O}yvind Palm and Kathrine Skarstein and Stolarczyk, \{Anna M.\} and Taylor, \{Kimberly E.\} and Maria Teruel and Elke Theander and Swamy Venuturupalli and Wallace, \{Daniel J.\} and Grundahl, \{Kiely M.\} and Hefner, \{Kimberly S.\} and Lida Radfar and Lewis, \{David M.\} and Stone, \{Donald U.\} and Kaufman, \{C. Erick\} and Brennan, \{Michael T.\} and Guthridge, \{Joel M.\} and James, \{Judith A.\} and Scofield, \{R. Hal\} and Gaffney, \{Patrick M.\} and Criswell, \{Lindsey A.\} and Roland Jonsson and Ng, \{Wan Fai\}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-30773-y",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells. / PRECISESADS Clinical Consortium; Sjögren’s International Collaborative Clinical Alliance (SICCA); UK primary Sjögren's Syndrome Registry.
In: Nature Communications, Vol. 13, No. 1, 4287, 12.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

AU - PRECISESADS Clinical Consortium

AU - Sjögren’s International Collaborative Clinical Alliance (SICCA)

AU - UK primary Sjögren's Syndrome Registry

AU - Khatri, Bhuwan

AU - Tessneer, Kandice L.

AU - Rasmussen, Astrid

AU - Aghakhanian, Farhang

AU - Reksten, Tove Ragna

AU - Adler, Adam

AU - Alevizos, Ilias

AU - Anaya, Juan Manuel

AU - Aqrawi, Lara A.

AU - Baecklund, Eva

AU - Brun, Johan G.

AU - Bucher, Sara Magnusson

AU - Eloranta, Maija Leena

AU - Engelke, Fiona

AU - Forsblad-d’Elia, Helena

AU - Glenn, Stuart B.

AU - Hammenfors, Daniel

AU - Imgenberg-Kreuz, Juliana

AU - Jensen, Janicke Liaaen

AU - Johnsen, Svein Joar Auglænd

AU - Jonsson, Malin V.

AU - Kvarnström, Marika

AU - Kelly, Jennifer A.

AU - Li, He

AU - Mandl, Thomas

AU - Martín, Javier

AU - Nocturne, Gaétane

AU - Norheim, Katrine Brække

AU - Palm, Øyvind

AU - Skarstein, Kathrine

AU - Stolarczyk, Anna M.

AU - Taylor, Kimberly E.

AU - Teruel, Maria

AU - Theander, Elke

AU - Venuturupalli, Swamy

AU - Wallace, Daniel J.

AU - Grundahl, Kiely M.

AU - Hefner, Kimberly S.

AU - Radfar, Lida

AU - Lewis, David M.

AU - Stone, Donald U.

AU - Kaufman, C. Erick

AU - Brennan, Michael T.

AU - Guthridge, Joel M.

AU - James, Judith A.

AU - Scofield, R. Hal

AU - Gaffney, Patrick M.

AU - Criswell, Lindsey A.

AU - Jonsson, Roland

AU - Ng, Wan Fai

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85124380336

U2 - 10.1038/s41467-022-30773-y

DO - 10.1038/s41467-022-30773-y

M3 - Article

C2 - 35896530

AN - SCOPUS:85124380336

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4287

ER -

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

Abstract

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