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Am J Hum Genet DOI:10.1086/444547

A high-density screen for linkage in multiple sclerosis.

Publication TypeJournal Article
Year of Publication2005
AuthorsSawcer, S, Ban, M, Maranian, M, Yeo, TWai, Compston, A, Kirby, A, Daly, MJ, De Jager, PL, Walsh, E, Lander, ES, Rioux, JD, Hafler, DA, Ivinson, A, Rimmler, J, Gregory, SG, Schmidt, S, Pericak-Vance, MA, Akesson, E, Hillert, J, Datta, P, Oturai, A, Ryder, LP, Harbo, HF, Spurkland, A, Myhr, K-M, Laaksonen, M, Booth, D, Heard, R, Stewart, G, Lincoln, R, Barcellos, LF, Hauser, SL, Oksenberg, JR, Kenealy, SJ, Haines, JL
Corporate AuthorsInternational Multiple Sclerosis Genetics Consortium
JournalAm J Hum Genet
Volume77
Issue3
Pages454-67
Date Published2005 Sep
ISSN0002-9297
KeywordsAustralia, Chromosome Mapping, Chromosomes, Human, Europe, Family, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Genetic Testing, Genomics, Humans, Middle Aged, Multiple Sclerosis, United States
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63025-0
DOI10.1086/444547
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/16080120?dopt=Abstract

Alternate JournalAm. J. Hum. Genet.
PubMed ID16080120
PubMed Central IDPMC1226210
Grant ListU01 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