A second-generation genomic screen for multiple sclerosis.

Published

Journal Article

Multiple sclerosis (MS) is a debilitating neuroimmunological and neurodegenerative disorder. Despite substantial evidence for polygenic inheritance of the disease, the major histocompatibility complex is the only region that clearly and consistently demonstrates linkage and association in MS studies. The goal of this study was to identify additional chromosomal regions that harbor susceptibility genes for MS. With a panel of 390 microsatellite markers genotyped in 245 U.S. and French multiplex families (456 affected relative pairs), this is the largest genomic screen for MS conducted to date. Four regions met both of our primary criteria for further interest (heterogeneity LOD [HLOD] and Z scores >2.0): 1q (HLOD=2.17; Z=3.38), 6p (HLOD=4.21; Z=2.26), 9q (HLOD; Z=2.71), and 16p (HLOD=2.64; Z=2.05). Two additional regions met only the Z score criterion: 3q (Z=2.39) and 5q (Z=2.17). Further examination of the data by country (United States vs. France) identified one additional region demonstrating suggestive linkage in the U.S. subset (18p [HLOD=2.39]) and two additional regions generating suggestive linkage in the French subset (1p [HLOD=2.08] and 22q [HLOD=2.06]). Examination of the data by human leukocyte antigen (HLA)-DR2 stratification identified four additional regions demonstrating suggestive linkage: 2q (HLOD=3.09 in the U.S. DR2- families), 6q (HLOD=3.10 in the French DR2- families), 13q (HLOD=2.32 in all DR2+ families and HLOD=2.17 in the U.S. DR2+ families), and 16q (HLOD=2.32 in all DR2+ families and HLOD=2.13 in the U.S. DR2+ families). These data suggest several regions that warrant further investigation in the search for MS susceptibility genes.

Full Text

Duke Authors

Cited Authors

  • Kenealy, SJ; Babron, M-C; Bradford, Y; Schnetz-Boutaud, N; Haines, JL; Rimmler, JB; Schmidt, S; Pericak-Vance, MA; Barcellos, LF; Lincoln, RR; Oksenberg, JR; Hauser, SL; Clanet, M; Brassat, D; Edan, G; Yaouanq, J; Semana, G; Cournu-Rebeix, I; Lyon-Caen, O; Fontaine, B; American-French Multiple Sclerosis Genetics Group,

Published Date

  • December 2004

Published In

Volume / Issue

  • 75 / 6

Start / End Page

  • 1070 - 1078

PubMed ID

  • 15494893

Pubmed Central ID

  • 15494893

International Standard Serial Number (ISSN)

  • 0002-9297

Digital Object Identifier (DOI)

  • 10.1086/426459

Language

  • eng

Conference Location

  • United States