Ontology highlight
ABSTRACT: The goal of this study is to perform a comprehensive allelic and genotypic association analysis of the entire human genome
in multiple sclerosis. The recent definitive linkage genome screen demonstrated that there is no other MS risk gene with an
effect size anywhere near that of the MHC. However, linkage analysis is significantly hampered by reduced power in the face
of heterogeneity and requires multiplex families, which also hampers acquiring an appropriate sample size. In contrast,
genotyping 500K SNPs allows us to survey a significant amount of the genome (we estimate >70%) directly for allelic
or genotypic association. This uses the improved power of association analysis and can also take advantage
of the linkage disequilibrium relationships among SNPs to further increase power (e.g. haplotype analysis). Quality control
and data analysis are significant challenges. We will initially perform substantial QC checks and analyze the data using both
TDT and AFBAC approaches. Multigenic interactions will also be tested using MDR.
PROVIDER: phs000139.v1.p1 | EGA |
REPOSITORIES: EGA
Hafler David A DA Compston Alastair A Sawcer Stephen S Lander Eric S ES Daly Mark J MJ De Jager Philip L PL de Bakker Paul I W PI Gabriel Stacey B SB Mirel Daniel B DB Ivinson Adrian J AJ Pericak-Vance Margaret A MA Gregory Simon G SG Rioux John D JD McCauley Jacob L JL Haines Jonathan L JL Barcellos Lisa F LF Cree Bruce B Oksenberg Jorge R JR Hauser Stephen L SL
The New England journal of medicine 20070729 9
<h4>Background</h4>Multiple sclerosis has a clinically significant heritable component. We conducted a genomewide association study to identify alleles associated with the risk of multiple sclerosis.<h4>Methods</h4>We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another 609 family trios, 2322 case subjects, and 789 control subjects and u ...[more]