High inbreeding in the Faroe Islands does not appear to constitute a risk factor for multiple sclerosis.
BACKGROUND
Large population-based genome-wide association studies have identified several multiple sclerosis (MS) genetic risk variants, but the existing missing heritability warrants different strategies. Isolated populations offer an alternative way of searching for rare genetic variants and evaluating the possible role of consanguinity in the development of MS. Studies of consanguinity and MS risk have yielded conflicting results.


OBJECTIVE
In this study we investigated the role of consanguinity on MS risk in the relatively isolated Faroe Islands, which have a presumed high level of inbreeding.


METHODS
A total of 29 cases and 28 matched controls were genotyped and assessed for inbreeding coefficients, number of runs of homozygosity (ROH) at different lengths and observed number of homozygotes as measures of relatedness. Parametric and non-parametric statistical models were applied.


RESULTS
Both cases and controls exhibited considerable relatedness demonstrated by very high inbreeding coefficients, large number of observed homozygotes and many long ROH. However, apart from the number of ROH ≥ 2.5 mega base pairs, no significant differences between the two groups were observed.


CONCLUSIONS
Overall, no significant difference between cases and controls were found, indicating that consanguinity in itself does not appear to be an important risk factor for MS in the population of the Faroe Islands.
Institute of Regional Health Services Research, University of Southern Denmark, Denmark/MS Clinic of Southern Jutland (Sønderborg, Esbjerg, Vejle), Department of Neurology, Denmark/Torshavn National Hospital, Torshavn, Faroe Islands Odense Patient data explorative network (OPEN) sbinzer@health.sdu.dk.
S
S
Binzer
Karolinska Institute, Clinical Neuroscience, Division of Neurology, Department of Clinical Neuroscience, Sweden.
K
K
Imrell
Institute of Regional Health Services Research, University of Southern Denmark, Denmark.
M
M
Binzer
Institute of Regional Health Services Research, University of Southern Denmark, Denmark/Odense Patient data Explorative Network (OPEN), Odense University Hospital, Denmark.
K O
KO
Kyvik
Karolinska Institute, Clinical Neuroscience, Division of Neurology, Department of Clinical Neuroscience, Sweden.
J
J
Hillert
Institute of Regional Health Services Research, University of Southern Denmark, Denmark/MS Clinic of Southern Jutland (Sønderborg, Esbjerg, Vejle), Department of Neurology, Denmark.
E
E
Stenager
D000328:Adult; D000368:Aged; D003241:Consanguinity; D004247:DNA / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007178:Inbreeding / Q000706:statistics & numerical data*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D012042:Registries; D012307:Risk Factors
D004247:DNA
Faroe Islands; Multiple sclerosis; genetics; inbreeding; risk factors; runs of homozygosity