TY - JOUR
T1 - Oligoclonal bands and age at onset correlate with genetic risk score in multiple sclerosis
AU - Harbo, Hanne F.
AU - Isobe, Noriko
AU - Berg-Hansen, Pål
AU - Bos, Steffan D.
AU - Caillier, Stacy J.
AU - Gustavsen, Marte W.
AU - Mero, Inger Lise
AU - Celius, Elisabeth Gulowsen
AU - Hauser, Stephen L.
AU - Oksenberg, Jorge R.
AU - Gourraud, Pierre Antoine
N1 - Funding Information:
This work was supported by the Research Council of Norway (HFH grant numbers 189639 and 196776). Genotyping of the Oslo cohort was partly supported by Novartis Norway (unrestricted grant). Data collection and genotyping in the US was supported by the US National Institute of Health (grant number RO1-NS26799). Postdoctoral fellow NI was supported by the Japan Society for Promotion of Science. PAG was supported by the Nancy Davis Foundation for Multiple Sclerosis (Junior Faculty Award).
PY - 2014/5
Y1 - 2014/5
N2 - Background: Many genetic risk variants are now well established in multiple sclerosis (MS), but the impact on clinical phenotypes is unclear. Objective: To investigate the impact of established MS genetic risk variants on MS phenotypes, in well-characterized MS cohorts. Methods: Norwegian MS patients (n = 639) and healthy controls (n = 530) were successfully genotyped for 61 established MS-associated single nucleotide polymorphisms (SNPs). Data including and excluding Major Histocompatibility Complex (MHC) markers were summed to a MS Genetic Burden (MSGB) score. Study replication was performed in a cohort of white American MS patients (n = 1997) and controls (n = 708). Results: The total human leukocyte antigen (HLA) and the non-HLA MSGB scores were significantly higher in MS patients than in controls, in both cohorts (P 10 -22). MS patients, with and without cerebrospinal fluid (CSF) oligoclonal bands (OCBs), had a higher MSGB score than the controls; the OCB-positive patients had a slightly higher MSGB than the OCB-negative patients. An early age at symptom onset (AAO) also correlated with a higher MSGB score, in both cohorts. Conclusion: The MSGB score was associated with specific clinical MS characteristics, such as OCBs and AAO. This study underlines the need for well-characterized, large cohorts of MS patients, and the usefulness of summarizing multiple genetic risk factors of modest effect size in genotype-phenotype analyses.
AB - Background: Many genetic risk variants are now well established in multiple sclerosis (MS), but the impact on clinical phenotypes is unclear. Objective: To investigate the impact of established MS genetic risk variants on MS phenotypes, in well-characterized MS cohorts. Methods: Norwegian MS patients (n = 639) and healthy controls (n = 530) were successfully genotyped for 61 established MS-associated single nucleotide polymorphisms (SNPs). Data including and excluding Major Histocompatibility Complex (MHC) markers were summed to a MS Genetic Burden (MSGB) score. Study replication was performed in a cohort of white American MS patients (n = 1997) and controls (n = 708). Results: The total human leukocyte antigen (HLA) and the non-HLA MSGB scores were significantly higher in MS patients than in controls, in both cohorts (P 10 -22). MS patients, with and without cerebrospinal fluid (CSF) oligoclonal bands (OCBs), had a higher MSGB score than the controls; the OCB-positive patients had a slightly higher MSGB than the OCB-negative patients. An early age at symptom onset (AAO) also correlated with a higher MSGB score, in both cohorts. Conclusion: The MSGB score was associated with specific clinical MS characteristics, such as OCBs and AAO. This study underlines the need for well-characterized, large cohorts of MS patients, and the usefulness of summarizing multiple genetic risk factors of modest effect size in genotype-phenotype analyses.
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U2 - 10.1177/1352458513506503
DO - 10.1177/1352458513506503
M3 - Article
C2 - 24099750
AN - SCOPUS:84899048957
SN - 1352-4585
VL - 20
SP - 660
EP - 668
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
IS - 6
ER -
