Class II HLA interactions modulate genetic risk for multiple sclerosis
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Class II HLA interactions modulate genetic risk for multiple sclerosis. / Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H; Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D'Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Lar Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen wcer; McVean, Gil; International IBD Genetics Consortium (IIBDGC).
In: NAT GENET, Vol. 47, No. 10, 10.2015, p. 1107-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - Lar Fugger, Lars
AU - Goris, An
AU - Gourraud, Pierre-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 - Haines, Jonathan L
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 wcer
AU - McVean, Gil
AU - International IBD Genetics Consortium (IIBDGC)
PY - 2015/10
Y1 - 2015/10
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.
KW - Alleles
KW - Epistasis, Genetic
KW - Genetic Predisposition to Disease
KW - Histocompatibility Antigens Class II
KW - Humans
KW - Multiple Sclerosis
KW - Polymorphism, Single Nucleotide
U2 - 10.1038/ng.3395
DO - 10.1038/ng.3395
M3 - SCORING: Journal article
C2 - 26343388
VL - 47
SP - 1107
EP - 1113
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 10
ER -