@article{696c75a915b945edab8bd28355f107ed,
title = "Investigating multiple sclerosis genetic susceptibility on the founder population of east-central Sardinia via association and linkage analysis of immune-related loci",
abstract = "Background: A wealth of single-nucleotide polymorphisms (SNPs) responsible for multiple sclerosis (MS) susceptibility have been identified; however, they explain only a fraction of MS heritability. Objectives: We contributed to discovery of new MS susceptibility SNPs by studying a founder population with high MS prevalence. Methods: We analyzed ImmunoChip data from 15 multiplex families and 94 unrelated controls from the Nuoro Province, Sardinia, Italy. We tested each SNP for both association and linkage with MS, the linkage being explored in terms of identity-by-descent (IBD) sharing excess and using gene dropping to compute a corresponding empirical p-value. By targeting regions that are both associated and in linkage with MS, we increase chances of identifying interesting genomic regions. Results: We identified 486 MS-associated (p < 1 × 10–4) and 18,426 MS-linked (p < 0.05) SNPs. A total of 111 loci were both linked and associated with MS, 18 of them pointing to 14 non-major histocompatibility complex (MHC) genes, and 93 of them located in the MHC region. Conclusion: We discovered new suggestive signals and confirmed some previously identified ones. We believe this to represent a significant step toward an understanding of the genetic basis of MS.",
keywords = "Multiple sclerosis, association, founder population, identity-by-descent sharing, pedigree",
author = "Teresa Fazia and Roberta Pastorino and Luisa Foco and Lide Han and Mark Abney and Ashley Beecham and Athena Hadjixenofontos and Hui Guo and Davide Gentilini and Charalampos Papachristou and Bitti, {Pier Paolo} and Anna Ticca and Carlo Berzuini and McCauley, {Jacob L.} and Luisa Bernardinelli",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by MIMOmics European Collaborative Project (FP7-305280), as part of the HEALTH-2012-INNOVATION scheme, and by FISM—Fondazione Italiana Sclerosi Multipla (Cod. 2009//R//2) and by Fondazione Cariplo (grant no. 2009-2528). Funding Information: We wish to thank the patients, their relatives, and all the volunteers who donated their samples. We gratefully acknowledge Dr Valeria Saddi, Dr Marialuisa Piras, and all the ascertainment team in Nuoro. We thank the Center for Genome Technology within the University of Miami John P. Hussman Institute for Human Genomics for generating the genotype data for this project. The study was approved by the ethics committee of the Azienda Sanitaria of Nuoro and was conducted in conformity with the 1954 Declaration of Helsinki in its currently applicable version and applicable Italian laws. All study participants gave written informed consent. T.F. and R.P. contributed equally to this work. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by MIMOmics European Collaborative Project (FP7-305280), as part of the HEALTH-2012-INNOVATION scheme, and by FISM?Fondazione Italiana Sclerosi Multipla (Cod. 2009//R//2) and by Fondazione Cariplo (grant no. 2009-2528). Publisher Copyright: {\textcopyright} The Author(s), 2017.",
year = "2018",
month = dec,
day = "1",
doi = "10.1177/1352458517732841",
language = "English (US)",
volume = "24",
pages = "1815--1824",
journal = "Multiple Sclerosis",
issn = "1352-4585",
publisher = "SAGE Publications Ltd",
number = "14",
}