Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia.
BACKGROUND
The list of genomic loci associated with multiple sclerosis (MS) susceptibility outside the major histocompatibility complex (MHC) in patients of Northern European (NE) ancestry has increased to 103. Despite the extraordinarily high MS prevalence in the isolated Sardinian population, the contribution of genetic risk factors to MS in Sardinia is largely not understood.


OBJECTIVE
The objective of this paper is to examine the relevance of non-MHC MS susceptibility variants in Sardinia.


METHODS
We examined a log-additive MS-specific genetic burden score (MSGB) using 110 NE-derived risk alleles in a dataset of 75 Sardinian cases, 346 Sardinian controls and 177 cases and 1967 controls from the United States (US).


RESULTS
Sardinian cases demonstrate a heavier non-MHC MSGB load than Sardinian controls and US cases (p = 2E-06, p = 1E-06, respectively). Furthermore, Sardinian controls carry a heavier burden than US controls (p = 2E-14). Our results confirm the limited ability of the 110-SNP MSGB to predict disease status in Sardinia (AUROC = 0.629).


CONCLUSIONS
Risk alleles discovered in samples of NE ancestry are relevant to MS in Sardinia. Our results suggest a general enrichment of MS susceptibility alleles in Sardinians, encouraging the pursuit of further studies of MS in this population.
John P. Hussman Institute for Human Genomics and Dr John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, USA.
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Hadjixenofontos
Department of Neurology, School of Medicine, University of California at San Francisco, USA.
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Gourraud
Department of Neurology, School of Medicine, University of California at San Francisco, USA.
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Bakthavachalam
Department of Brain and Behavioral Sciences, University of Pavia, Italy.
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Foco
Divisione di Neurologia, Ospedale S. Francesco, Italy.
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Ticca
Immunohaematology and Blood Transfusion Department, Ospedale S. Francesco, Italy.
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Bitti
Department of Brain and Behavioral Sciences, University of Pavia, Italy.
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Pastorino
Department of Brain and Behavioral Sciences, University of Pavia, Italy/Department of Brain and Behavioral Sciences, University of Pavia, Italy Centre for Biostatistics, Institute of Population Health, University of Manchester, UK.
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Bernardinelli
John P. Hussman Institute for Human Genomics and Dr John T Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, USA jmccauley@med.miami.edu.
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McCauley
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002648:Child; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D012306:Risk; D014481:United States / Q000453:epidemiology; D055815:Young Adult
Multiple sclerosis; Sardinia; genetic burden; genetic risk; genetics