Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia

A Hadjixenofontos; P A Gourraud; V Bakthavachalam; L Foco; A Ticca; P Bitti; R Pastorino; L Bernardinelli; J L McCauley

doi:10.1177/1352458515581872

Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia

Mult Scler. 2015 Oct;21(11):1396-403. doi: 10.1177/1352458515581872. Epub 2015 Apr 28.

Authors

A Hadjixenofontos¹, P A Gourraud², V Bakthavachalam², L Foco³, A Ticca⁴, P Bitti⁵, R Pastorino³, L Bernardinelli⁶, J L McCauley⁷

Affiliations

¹ 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.
² Department of Neurology, School of Medicine, University of California at San Francisco, USA.
³ Department of Brain and Behavioral Sciences, University of Pavia, Italy.
⁴ Divisione di Neurologia, Ospedale S. Francesco, Italy.
⁵ Immunohaematology and Blood Transfusion Department, Ospedale S. Francesco, Italy.
⁶ 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.
⁷ 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.

PMID: 25921054
DOI: 10.1177/1352458515581872

Abstract

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.

Keywords: Multiple sclerosis; Sardinia; genetic burden; genetic risk; genetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age of Onset
Alleles
Child
Europe / epidemiology
Female
Genetic Predisposition to Disease*
Humans
Italy / epidemiology
Male
Middle Aged
Multiple Sclerosis / epidemiology*
Multiple Sclerosis / genetics*
Risk
United States / epidemiology
Young Adult