A high-density screen for linkage in multiple sclerosis.

Am J Hum Genet
Authors
Keywords
Abstract

To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis-associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology.

Year of Publication
2005
Journal
Am J Hum Genet
Volume
77
Issue
3
Pages
454-67
Date Published
2005 Sep
ISSN
0002-9297
URL
DOI
10.1086/444547
PubMed ID
16080120
PubMed Central ID
PMC1226210
Links
Grant list
U01 DK062432 / DK / NIDDK NIH HHS / United States
R01 DK064869 / DK / NIDDK NIH HHS / United States
P01 AI065687 / AI / NIAID NIH HHS / United States
NS032830 / NS / NINDS NIH HHS / United States
R01 NS032830 / NS / NINDS NIH HHS / United States
Wellcome Trust / United Kingdom
U19 AI067152 / AI / NIAID NIH HHS / United States