Evidence map›Paper›PMID 40884622›Full record

ArticleBiochemical genetics2026

Knockoff-Based Fine Mapping of MS-Associated SNPs in Sardinian Trios.

Giulia Nicole Baldrighi, Andrea Nova, Claus Thorn Ekstrøm, Maria Luisa Piras, Maria Valeria Saddi, Luisa Bernardinelli, Teresa Fazia

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Article in Biochemical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Giulia Nicole BaldrighiDepartment of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100, Pavia, Italy. giulianicole.baldrighi01@universitadipavia.it.ORCID http://orcid.org/0000-0001-8538-4768
Andrea NovaDepartment of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy.
Claus Thorn EkstrømDepartment of Public Health, University of Copenhagen, 1014, Copenhagen, Denmark.
Maria Luisa PirasUnità Operativa Neurologia, Stroke Unit, Ospedale S. Francesco - ASL 3 Nuoro, 08100, Nuoro, Italy.
Maria Valeria SaddiUnità Operativa Neurologia, Stroke Unit, Ospedale S. Francesco - ASL 3 Nuoro, 08100, Nuoro, Italy.
Luisa BernardinelliDepartment of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy.
Teresa FaziaDepartment of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genetic predisposition plays a key role in autoimmune and complex diseases such as multiple sclerosis (MS). However, identifying the specific variants or genomic regions responsible for disease susceptibility remains a significant challenge. In this study a family-based fine mapping approach was applied to analyze 142 trios, aiming to identify associated genetic variants linked to MS. The targeted genomic region resides within the 17:30,820,506-32,483,270 bp (Ch37/hg19), which includes the protein-coding gene ASIC2, previously implicated in MS and other neurological conditions, with surrounding genes comprising strongly correlated genetic variants to capture the broader signal from the region. Given the high prevalence of MS in Sardinia and the unique genetic characteristics of the Sardinian population, including reduced heterogeneity and extended linkage disequilibrium, we designed our study specifically within this population and focused on family-based data to enhance the power for detecting genetic signals, avoiding false discoveries. Genotype imputation found 2537 variants, which were then analyzed using the knockoff Trio method to identify loci associated with MS susceptibility. We found rs756787 (3'UTR of MYO1D) increased disease risk (OR 1.57, 95% CI [1.07-2.29], p = 0.02), while rs56175840 (intronic ASIC2) showed a protective effect (OR 0.17, 95% CI [0.04-0.74], p = 0.02), demonstrating the power of knockoff-based fine mapping in family datasets. Integrating LD-based expression and trait analyses helped reveal how rs756787 correlates with variants affecting genes involved in neurodegeneration and the immune response to Epstein-Barr virus, a known environmental factor implicated in MS pathogenesis. Our study highlights the effectiveness of knockoff-based fine mapping combined with expression-trait integration to identify genetic variants influencing MS risk in the Sardinian population.

Indexed as

Acid Sensing Ion ChannelsGenetic Predisposition to DiseaseMultiple SclerosisPolymorphism, Single NucleotideAdultChromosome MappingFemaleHumansItalyLinkage DisequilibriumMaleAcid Sensing Ion ChannelsComplex diseaseFamily-based designFine mappingKnockoff genotypesMultiple sclerosis

Identifiers

PMID40884622
PMCPMC13186870

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