Journal article

Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects

Nikolaos A Patsopoulos, Lisa F Barcellos, Rogier Q Hintzen, Catherine Schaefer, Cornelia M Van Duijn, Janelle A Noble, Towfique Raj, Pierre-Antoine Gourraud, Barbara E Stranger, Jorge Oksenberg, Tomas Olsson, Bruce V Taylor, Stephen Sawcer, David A Hafler, Mary Carrington, Philip L De Jager, Paul IW De Bakker



The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes in 5,091 cases and 9,595 controls. We identified 11 statistically independent effects overall: 6 HLA-DRB1 and one DPB1 alleles in class II, one HLA-A and two B alleles in class I, and one signal in a region spanning from MICB to LST1. This genomic segment does not contain any HLA class I or II genes..

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Awarded by NIH/NINDS

Awarded by NIH/NIAID

Awarded by Stockholm County Council

Awarded by Australian Research Council

Awarded by Frederick National Laboratory for Cancer Research

Awarded by Netherlands Organization for Scientific Research (NWO)

Awarded by National Institute for Health Research

Funding Acknowledgements

This investigation was supported (in part) by a Postdoctoral Fellowship from the National Multiple Sclerosis Society to NAP, and by R01NS049477, R01NS026799, NIH/NINDS R01NS049510, R01NS0495103, NIH/NIAID R01AI076544, Dutch MS Research foundation, Bibbi and Niels Jensens Foundation, The Swedish Brain Foundation and Swedish research council, Stockholm County Council (562183), Swedish Council for Working life and Social Research, Knut and Alice Wallenbergs foundation, MS research Australia (MSRA), John T. Reid Charitable Trusts, Trish MS Research Foundation and the Australian Research Council, under the Linkage Projects Scheme (LP0776744), the Cambridge NIHR Biomedical Research Centre. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. PLDJ is a Harry Weaver neuroscience scholar of the National MS Society (JF2138A1). PIWdB is the recipient of a VIDI Award from the Netherlands Organization for Scientific Research (NWO project 016.126.354). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.