Class II HLA interactions modulate genetic risk for multiple sclerosis

Loukas Moutsianas; Luke Jostins; Ashley H. Beecham; Alexander T. Dilthey; Dionysia K. Xifara; Maria Ban; Tejas S. Shah; Nikolaos A. Patsopoulos; Lars Alfredsson; Carl A. Anderson; Katherine E. Attfield; Sergio E. Baranzini; Jeffrey Barrett; Thomas M.C. Binder; David Booth; Dorothea Buck; Elisabeth G. Celius; Chris Cotsapas; Sandra D'Alfonso; Calliope A. Dendrou; Peter Donnelly; Bénédicte Dubois; Bertrand Fontaine; Lars Fugger; An Goris; Pierr Antoine Gourraud; Christiane Graetz; Bernhard Hemmer; Jan Hillert; Ingrid Kockum; Stephen Leslie; Christina M. Lill; Filippo Martinelli-Boneschi; Jorge R. Oksenberg; Tomas Olsson; Annette Oturai; Janna Saarela; Helle Bach SØndergaard; Anne Spurkland; Bruce Taylor; Juliane Winkelmann; Frauke Zipp; Jonathan L Haines; Margaret A. Pericak-Vance; Chris C.A. Spencer; Graeme Stewart; David A. Hafler; Adrian J. Ivinson; Hanne F. Harbo; Stephen L. Hauser; Philip L. De Jager; Alastair Compston; Jacob L. McCauley; Stephen Sawcer; Gil McVean

doi:10.1038/ng.3395

Class II HLA interactions modulate genetic risk for multiple sclerosis

Loukas Moutsianas, Luke Jostins, Ashley H. Beecham, Alexander T. Dilthey, Dionysia K. Xifara, Maria Ban, Tejas S. Shah, Nikolaos A. Patsopoulos, Lars Alfredsson, Carl A. Anderson, Katherine E. Attfield, Sergio E. Baranzini, Jeffrey Barrett, Thomas M.C. Binder, David Booth, Dorothea Buck, Elisabeth G. Celius, Chris Cotsapas, Sandra D'Alfonso, Calliope A. DendrouPeter Donnelly, Bénédicte Dubois, Bertrand Fontaine, Lars Fugger, An Goris, Pierr Antoine Gourraud, Christiane Graetz, Bernhard Hemmer, Jan Hillert, Ingrid Kockum, Stephen Leslie, Christina M. Lill, Filippo Martinelli-Boneschi, Jorge R. Oksenberg, Tomas Olsson, Annette Oturai, Janna Saarela, Helle Bach SØndergaard, Anne Spurkland, Bruce Taylor, Juliane Winkelmann, Frauke Zipp, Jonathan L Haines, Margaret A. Pericak-Vance, Chris C.A. Spencer, Graeme Stewart, David A. Hafler, Adrian J. Ivinson, Hanne F. Harbo, Stephen L. Hauser, Philip L. De Jager, Alastair Compston, Jacob L. McCauley, Stephen Sawcer, Gil McVean

Lehrstuhl für Neurogenetik (2015 — 2023)

Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung

268 Zitate (Scopus)

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.

Originalsprache	Englisch
Seiten (von - bis)	1107-1113
Seitenumfang	7
Fachzeitschrift	Nature Genetics
Jahrgang	47
Ausgabenummer	10
DOIs	https://doi.org/10.1038/ng.3395
Publikationsstatus	Veröffentlicht - 29 Sept. 2015

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10.1038/ng.3395

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Moutsianas, L., Jostins, L., Beecham, A. H., Dilthey, A. T., Xifara, D. K., Ban, M., Shah, T. S., Patsopoulos, N. A., Alfredsson, L., Anderson, C. A., Attfield, K. E., Baranzini, S. E., Barrett, J., Binder, T. M. C., Booth, D., Buck, D., Celius, E. G., Cotsapas, C., D'Alfonso, S., ... McVean, G. (2015). Class II HLA interactions modulate genetic risk for multiple sclerosis. Nature Genetics, 47(10), 1107-1113. https://doi.org/10.1038/ng.3395

@article{23632b14e89f4d9f91eb6b827902fb0e,

title = "Class II HLA interactions modulate genetic risk for multiple sclerosis",

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.",

author = "Loukas Moutsianas and Luke Jostins and Beecham, {Ashley H.} and Dilthey, {Alexander T.} and Xifara, {Dionysia K.} and Maria Ban and Shah, {Tejas S.} and Patsopoulos, {Nikolaos A.} and Lars Alfredsson and Anderson, {Carl A.} and Attfield, {Katherine E.} and Baranzini, {Sergio E.} and Jeffrey Barrett and Binder, {Thomas M.C.} and David Booth and Dorothea Buck and Celius, {Elisabeth G.} and Chris Cotsapas and Sandra D'Alfonso and Dendrou, {Calliope A.} and Peter Donnelly and B{\'e}n{\'e}dicte Dubois and Bertrand Fontaine and Lars Fugger and An Goris and Gourraud, {Pierr Antoine} and Christiane Graetz and Bernhard Hemmer and Jan Hillert and Ingrid Kockum and Stephen Leslie and Lill, {Christina M.} and Filippo Martinelli-Boneschi and Oksenberg, {Jorge R.} and Tomas Olsson and Annette Oturai and Janna Saarela and S{\O}ndergaard, {Helle Bach} and Anne Spurkland and Bruce Taylor and Juliane Winkelmann and Frauke Zipp and {L Haines}, Jonathan and Pericak-Vance, {Margaret A.} and Spencer, {Chris C.A.} and Graeme Stewart and Hafler, {David A.} and Ivinson, {Adrian J.} and Harbo, {Hanne F.} and Hauser, {Stephen L.} and {De Jager}, {Philip L.} and Alastair Compston and McCauley, {Jacob L.} and Stephen Sawcer and Gil McVean",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = sep,

day = "29",

doi = "10.1038/ng.3395",

language = "English",

volume = "47",

pages = "1107--1113",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Moutsianas, L, Jostins, L, Beecham, AH, Dilthey, AT, Xifara, DK, Ban, M, Shah, TS, Patsopoulos, NA, Alfredsson, L, Anderson, CA, Attfield, KE, Baranzini, SE, Barrett, J, Binder, TMC, Booth, D, Buck, D, Celius, EG, Cotsapas, C, D'Alfonso, S, Dendrou, CA, Donnelly, P, Dubois, B, Fontaine, B, Fugger, L, Goris, A, Gourraud, PA, Graetz, C, Hemmer, B, Hillert, J, Kockum, I, Leslie, S, Lill, CM, Martinelli-Boneschi, F, Oksenberg, JR, Olsson, T, Oturai, A, Saarela, J, SØndergaard, HB, Spurkland, A, Taylor, B, Winkelmann, J, Zipp, F, L Haines, J, Pericak-Vance, MA, Spencer, CCA, Stewart, G, Hafler, DA, Ivinson, AJ, Harbo, HF, Hauser, SL, De Jager, PL, Compston, A, McCauley, JL, Sawcer, S & McVean, G 2015, 'Class II HLA interactions modulate genetic risk for multiple sclerosis', Nature Genetics, Jg. 47, Nr. 10, S. 1107-1113. https://doi.org/10.1038/ng.3395

TY - JOUR

T1 - Class II HLA interactions modulate genetic risk for multiple sclerosis

AU - Moutsianas, Loukas

AU - Jostins, Luke

AU - Beecham, Ashley H.

AU - Dilthey, Alexander T.

AU - Xifara, Dionysia K.

AU - Ban, Maria

AU - Shah, Tejas S.

AU - Patsopoulos, Nikolaos A.

AU - Alfredsson, Lars

AU - Anderson, Carl A.

AU - Attfield, Katherine E.

AU - Baranzini, Sergio E.

AU - Barrett, Jeffrey

AU - Binder, Thomas M.C.

AU - Booth, David

AU - Buck, Dorothea

AU - Celius, Elisabeth G.

AU - Cotsapas, Chris

AU - D'Alfonso, Sandra

AU - Dendrou, Calliope A.

AU - Donnelly, Peter

AU - Dubois, Bénédicte

AU - Fontaine, Bertrand

AU - Fugger, Lars

AU - Goris, An

AU - Gourraud, Pierr Antoine

AU - Graetz, Christiane

AU - Hemmer, Bernhard

AU - Hillert, Jan

AU - Kockum, Ingrid

AU - Leslie, Stephen

AU - Lill, Christina M.

AU - Martinelli-Boneschi, Filippo

AU - Oksenberg, Jorge R.

AU - Olsson, Tomas

AU - Oturai, Annette

AU - Saarela, Janna

AU - SØndergaard, Helle Bach

AU - Spurkland, Anne

AU - Taylor, Bruce

AU - Winkelmann, Juliane

AU - Zipp, Frauke

AU - L Haines, Jonathan

AU - Pericak-Vance, Margaret A.

AU - Spencer, Chris C.A.

AU - Stewart, Graeme

AU - Hafler, David A.

AU - Ivinson, Adrian J.

AU - Harbo, Hanne F.

AU - Hauser, Stephen L.

AU - De Jager, Philip L.

AU - Compston, Alastair

AU - McCauley, Jacob L.

AU - Sawcer, Stephen

AU - McVean, Gil

PY - 2015/9/29

Y1 - 2015/9/29

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.3395

DO - 10.1038/ng.3395

M3 - Article

C2 - 26343388

AN - SCOPUS:84942981489

SN - 1061-4036

VL - 47

SP - 1107

EP - 1113

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Class II HLA interactions modulate genetic risk for multiple sclerosis

Abstract

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