Class II HLA interactions modulate genetic risk for multiple sclerosis

Nature Genetics
Loukas MoutsianasGil McVean

Abstract

Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles.

References

Jun 3, 1972·Lancet·C JersildT Fog
Aug 12, 2000·Annals of Neurology·T MastermanJ Hillert
Sep 24, 2002·Nature Immunology·Heather L E LangLars Fugger
Jun 3, 2005·Human Molecular Genetics·David A DymentGeorge C Ebers
Aug 5, 2005·American Journal of Human Genetics·Stephen SawcerUNKNOWN International Multiple Sclerosis Genetics Consortium
Aug 15, 2006·Human Molecular Genetics·Lisa F BarcellosJorge R Oksenberg
Jul 31, 2007·The New England Journal of Medicine·UNKNOWN International Multiple Sclerosis Genetics ConsortiumStephen L Hauser
Jan 9, 2008·American Journal of Human Genetics·Stephen LeslieGil McVean
Nov 18, 2008·Human Molecular Genetics·Sergio E BaranziniJorge R Oksenberg
Apr 22, 2009·Proceedings of the National Academy of Sciences of the United States of America·Matthew R LincolnGeorge C Ebers
Jun 16, 2009·Nature Genetics·UNKNOWN Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
May 11, 2010·Nature Genetics·Serena SannaFrancesco Cucca
Oct 19, 2010·Nature Genetics·UNKNOWN Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2Richard C Trembath
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Feb 9, 2011·Bioinformatics·Alexander T DiltheyGil McVean
Feb 10, 2011·Brain : a Journal of Neurology·Anna Karin HedströmLars Alfredsson
Jul 12, 2011·Nature Genetics·David M EvansUNKNOWN Wellcome Trust Case Control Consortium 2 (WTCCC2)
Aug 13, 2011·Nature·UNKNOWN International Multiple Sclerosis Genetics ConsortiumAlastair Compston
Dec 23, 2011·Annals of Neurology·Nikolaos A PatsopoulosPaul I W de Bakker
Mar 6, 2013·PLoS Computational Biology·Alexander DiltheyGil McVean
Oct 1, 2013·Nature Genetics·UNKNOWN International Multiple Sclerosis Genetics Consortium (IMSGC)Jacob L McCauley

❮ Previous
Next ❯

Citations

Mar 8, 2016·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S D BosH F Harbo
Oct 28, 2015·Nature Reviews. Genetics·Andrew R HarperEric J Topol
Jun 18, 2016·International Journal of Molecular Sciences·Teresa Maria CreanzaNicola Ancona
Sep 10, 2016·Journal of Neuroimmunology·C BoiocchiR Bergamaschi
Aug 23, 2016·Molecular and Cellular Probes·Vilija G Jokubaitis, Helmut Butzkueven
Nov 1, 2016·Acta neurologica Belgica·Andreas P LysandropoulosMichel Toungouz
Nov 8, 2016·Molecular and Cellular Probes·Christina M Lill
Dec 10, 2016·Nature Reviews. Neurology·Tomas OlssonLars Alfredsson
Aug 26, 2016·Journal of Neurology, Neurosurgery, and Psychiatry·Gongbu PanBruce V Taylor
Dec 25, 2016·Briefings in Bioinformatics·Francesco PappalardoSanto Motta
Apr 22, 2017·Multiple Sclerosis and Related Disorders·Helle Bach SøndergaardAnnette Bang Oturai
May 12, 2017·Science Translational Medicine·Jason H KarnesJoshua C Denny
Jan 3, 2018·Nature Reviews. Immunology·Calliope A DendrouLars Fugger
Jan 24, 2018·Brain : a Journal of Neurology·Ide SmetsStephen Sawcer
Feb 14, 2018·The Journal of Clinical Investigation·David A OstrovAaron W Michels
Mar 29, 2018·Journal of Translational Medicine·Simone AgostiniMario Clerici
Feb 16, 2018·Journal of Neuroscience Research·Ivana BjelobabaIrena Lavrnja
Apr 24, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Lisa E CrearyMarcelo A Fernández-Viňa
Jan 30, 2018·Annals of the New York Academy of Sciences·Olga MatveevaMarkus Kleinewietfeld
Jul 30, 2017·Physiological Genomics·Galina Y ZheleznyakovaLara Kular
Jan 6, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Kelly HilvenBénédicte Dubois
Jan 9, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Ester Canto, Jorge R Oksenberg
Feb 15, 2018·Cold Spring Harbor Perspectives in Medicine·Nikolaos A Patsopoulos
Aug 3, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Eva Rosa PetersenAnnette Bang Oturai
Sep 27, 2018·Multiple Sclerosis : Clinical and Laboratory Research·Anna K Hedström
Jul 8, 2016·Science Advances·Till F M AndlauerBertram Müller-Myhsok
Oct 10, 2018·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·R Dobson, G Giovannoni
May 8, 2018·Cold Spring Harbor Perspectives in Medicine·Lars Alfredsson, Tomas Olsson
Nov 20, 2016·Nature Reviews. Neurology·Calliope A DendrouLars Fugger
Feb 4, 2016·Nature Communications·Ragnar P KristjanssonKari Stefansson
Jun 5, 2019·Continuum : Lifelong Learning in Neurology·Bardia Nourbakhsh, Ellen M Mowry
Jun 22, 2019·Stroke; a Journal of Cerebral Circulation·Robin B BrownHugh S Markus
Jul 18, 2019·International Journal of Immunogenetics·Laura PisapiaGiovanna Del Pozzo
Jul 11, 2019·Brain : a Journal of Neurology·Kathryn C FitzgeraldPeter A Calabresi
Oct 2, 2019·Multiple Sclerosis : Clinical and Laboratory Research·Anna Karin HedströmLars Alfredsson
Aug 6, 2017·Clinical Reviews in Allergy & Immunology·Kyle T AmberLuca Borradori
Oct 9, 2019·Epigenomics·Eleftheria TheodoropoulouMaja Jagodic

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.