Replication Analysis Identifies TYK2 As a Multiple Sclerosis Susceptibility Factor

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2009 Mar 19

PMID 19293837

Citations 64

Authors

Maria Ban

An Goris

Aslaug R Lorentzen

Amie Baker

Tania Mihalova

Gillian Ingram

David R Booth

Robert N Heard

Graeme J Stewart

Elke Bogaert

Benedicte Dubois

Hanne F Harbo

Elisabeth G Celius

Anne Spurkland

Richard Strange

Clive Hawkins

Neil P Robertson

Frank Dudbridge

James Wason

Philip L De Jager

David Hafler

John D Rioux

Adrian J Ivinson

Jacob L McCauley

Margaret Pericak-Vance

Jorge R Oksenberg

Stephen L Hauser

David Sexton

Jonathan Haines

Stephen Sawcer

Alastair Compston

Affiliations

Soon will be listed here.

Abstract

In a recent genome-wide association study (GWAS) based on 12,374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis combining all available data, we found that evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P=2.7 x 10(-6), odds ratio=1.32 (1.17-1.47)). This single nucleotide polymorphism results in an amino acid substitution (proline to alanine) in the kinase domain of TYK2, which is predicted to influence the levels of phosphorylation and therefore activity of the protein and so is likely to have a functional role in multiple sclerosis.

Citing Articles

High-Resolution Structure of RNA G-Quadruplex Containing Unique Structural Motifs Originating from the 5'-UTR of Human Tyrosine Kinase 2 (TYK2).

Orehova M, Plavec J, Kocman V ACS Omega. 2024; 9(6):7215-7229.

PMID: 38371751 PMC: 10870306. DOI: 10.1021/acsomega.3c09592.

Novel Small Molecule Tyrosine Kinase 2 Pseudokinase Ligands Block Cytokine-Induced TYK2-Mediated Signaling Pathways.

Zhou Y, Li X, Shen R, Wang X, Zhang F, Liu S Front Immunol. 2022; 13:884399.

PMID: 35693820 PMC: 9186491. DOI: 10.3389/fimmu.2022.884399.

A Phenome-Wide Association Study of genes associated with COVID-19 severity reveals shared genetics with complex diseases in the Million Veteran Program.

Verma A, Tsao N, Thomann L, Ho Y, Iyengar S, Luoh S PLoS Genet. 2022; 18(4):e1010113.

PMID: 35482673 PMC: 9049369. DOI: 10.1371/journal.pgen.1010113.

Borrelia burgdorferi Is a Poor Inducer of Gamma Interferon: Amplification Induced by Interleukin-12.

van de Schoor F, Vrijmoeth H, Brouwer M, Ter Hofstede H, Lemmers H, Dijkstra H Infect Immun. 2022; 90(3):e0055821.

PMID: 35130450 PMC: 8929378. DOI: 10.1128/iai.00558-21.

Association of TYK2 polymorphisms with autoimmune diseases: A comprehensive and updated systematic review with meta-analysis.

Pellenz F, Dieter C, Lemos N, Bauer A, Marmontel de Souza B, Crispim D Genet Mol Biol. 2021; 44(2):e20200425.

PMID: 33949620 PMC: 8097517. DOI: 10.1590/1678-4685-GMB-2020-0425.

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