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, Jacob L McCauley

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1396-1403
Number of pages8
JournalMultiple Sclerosis
Volume21
Issue number11
DOIs
StatePublished - 2015

Fingerprint

Italy
Multiple Sclerosis
Alleles
Major Histocompatibility Complex
Population Genetics
Single Nucleotide Polymorphism
Population

Keywords

  • Genetic burden
  • Genetic risk
  • Genetics
  • Multiple sclerosis
  • Sardinia

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Hadjixenofontos, A., Gourraud, P. A., Bakthavachalam, V., Foco, L., Ticca, A., Bitti, P., ... McCauley, J. L. (2015). Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia. Multiple Sclerosis, 21(11), 1396-1403. https://doi.org/10.1177/1352458515581872

Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia. / Hadjixenofontos, A.; Gourraud, P. A.; Bakthavachalam, V.; Foco, L.; Ticca, A.; Bitti, P.; Pastorino, R.; Bernardinelli, L.; McCauley, Jacob L.

In: Multiple Sclerosis, Vol. 21, No. 11, 2015, p. 1396-1403.

Research output: Contribution to journalArticle

Hadjixenofontos, A, Gourraud, PA, Bakthavachalam, V, Foco, L, Ticca, A, Bitti, P, Pastorino, R, Bernardinelli, L & McCauley, JL 2015, 'Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia', Multiple Sclerosis, vol. 21, no. 11, pp. 1396-1403. https://doi.org/10.1177/1352458515581872
Hadjixenofontos A, Gourraud PA, Bakthavachalam V, Foco L, Ticca A, Bitti P et al. Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia. Multiple Sclerosis. 2015;21(11):1396-1403. https://doi.org/10.1177/1352458515581872
Hadjixenofontos, A. ; Gourraud, P. A. ; Bakthavachalam, V. ; Foco, L. ; Ticca, A. ; Bitti, P. ; Pastorino, R. ; Bernardinelli, L. ; McCauley, Jacob L. / Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia. In: Multiple Sclerosis. 2015 ; Vol. 21, No. 11. pp. 1396-1403.
@article{7b22fc8638bf4fe4ade2eeaab9161bb9,
title = "Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia",
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 = "Genetic burden, Genetic risk, Genetics, Multiple sclerosis, Sardinia",
author = "A. Hadjixenofontos and Gourraud, {P. A.} and V. Bakthavachalam and L. Foco and A. Ticca and P. Bitti and R. Pastorino and L. Bernardinelli and McCauley, {Jacob L}",
year = "2015",
doi = "10.1177/1352458515581872",
language = "English (US)",
volume = "21",
pages = "1396--1403",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "11",

}

TY - JOUR

T1 - Enrichment for Northern European-derived multiple sclerosis risk alleles in Sardinia

AU - Hadjixenofontos, A.

AU - Gourraud, P. A.

AU - Bakthavachalam, V.

AU - Foco, L.

AU - Ticca, A.

AU - Bitti, P.

AU - Pastorino, R.

AU - Bernardinelli, L.

AU - McCauley, Jacob L

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Genetic burden

KW - Genetic risk

KW - Genetics

KW - Multiple sclerosis

KW - Sardinia

UR - http://www.scopus.com/inward/record.url?scp=84986001282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986001282&partnerID=8YFLogxK

U2 - 10.1177/1352458515581872

DO - 10.1177/1352458515581872

M3 - Article

C2 - 25921054

AN - SCOPUS:84943173068

VL - 21

SP - 1396

EP - 1403

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 11

ER -