title: Identity-by-descent mapping in a Scandinavian multiple sclerosis cohort.
abstract: In an attempt to map chromosomal regions carrying rare gene variants contributing to the risk of multiple sclerosis (MS), we identified segments shared identical-by-descent (IBD) using the software BEAGLE 4.0's refined IBD analysis. IBD mapping aims at identifying segments inherited from a common ancestor and shared more frequently in case-case pairs. A total of 2106 MS patients of Nordic origin and 624 matched controls were genotyped on Illumina Human Quad 660 chip and an additional 1352 ethnically matched controls typed on Illumina HumanHap 550 and Illumina 1M were added. The quality control left a total of 441 731 markers for the analysis. After identification of segments shared by descent and significance testing, a filter function for markers with low IBD sharing was applied. Four regions on chromosomes 5, 9, 14 and 19 were found to be significantly associated with the risk for MS. However, all markers but for one were located telomerically, including the very distal markers. For methodological reasons, such segments have a low sharing of IBD signals and are prone to be false positives. One marker on chromosome 19 reached genome-wide significance and was not one of the distal markers. This marker was located within the GNA11 gene, which contains no previous association with MS. We conclude that IBD mapping is not sufficiently powered to identify MS risk loci even in ethnically relatively homogenous populations, or that alternatively rare variants are not adequately present.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helga
authors.initials: H
authors.lastname: Westerlind
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Imrell
authors.affiliation: 1] Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden [2] Department of Mathematics, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Ryan
authors.initials: R
authors.lastname: Ramanujam
authors.affiliation: 1] KG Jebsen Centre for MS Research, Department of Clinical Medicine, University of Bergen, Bergen, Norway [2] Norwegian Multiple Sclerosis Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Elisabeth Gulowsen
authors.initials: EG
authors.lastname: Celius
authors.affiliation: 1] Department of Neurology, Oslo University Hospital, Oslo, Norway [2] Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.affiliation: Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Annette Bang
authors.initials: AB
authors.lastname: Oturai
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Insitute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.affiliation: Department of Mathematics, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Timo
authors.initials: T
authors.lastname: Koski
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
mesh_terms: D002874:Chromosome Mapping; D015331:Cohort Studies; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D009154:Mutation; D012537:Scandinavian and Nordic Countries
chemical_list: D005819:Genetic Markers