Increased burden of rare variants in GWAS associated genes in familial multiple sclerosis

Turk, Aleksander (avtor), Maver, Aleš (avtor), Juvan, Peter (avtor), Drulović, Jelena (avtor), Mesaros, Sarlota (avtor), Novaković, Ivana (avtor), Starčević-Čizmarević, Nada (avtor), Ristić, Smiljana (avtor), Stanković Matić, Ivana (avtor), Peterlin, Borut (avtor)

Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease affecting the central nervous system with many known genetic risk factors. Although genome-wide association studies (GWAS) have identified common genetic variants with small effects associated with MS, the role of rare variants with large effects in MS aetiology remains underexplored. We hypothesized that rare variants in MS-associated genes from GWAS studies (GWAS-associated genes) are more likely to contribute to familial MS (FMS) risk than to sporadic MS (SMS). Therefore, we aimed to assess the burden of rare, predicted pathogenic (RPP) variants in GWAS-associated genes in FMS and SMS patients compared to controls. Rare genetic variants in 111 GWAS-associated genes were assessed in 87 FMS, 89 SMS and 3866 control cases. We demonstrate that RPP variants were significantly overrepresented in the FMS cohort whereas their frequency was not increased in the SMS cohort compared to controls (p-values 5.27 × 10− 74 and 1.00, respectively). Six genes (ALPK2, ANKRD55, INTS8, IQCB1, JADE2, and MALT1) significantly contributed to the burden of RPP in the FMS group. We conclude that rare variants in genes identified by GWAS might contribute to the genetic predisposition of familial MS patients.

• Jezik: Angleški jezik
• Ključne besede: multiple sclerosis, burden analysis, whole exome sequencing (WES), rare variants, rare pathological changes, candidate genes
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 6 str.
• Številčenje: Vol. 15, art. 21200
• PID: 20.500.12556/RUL-182521
• UDK: 616.832-004
• ISSN pri članku: 2045-2322
• DOI: 10.1038/s41598-025-04741-7
• COBISS.SI-ID: 241991939
• Datum objave v RUL: 14.05.2026

Gradivo je del revije

• Naslov: Scientific reports
• Skrajšan naslov: Sci. rep.
• Založnik: Nature Publishing Group
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0326
• Naslov: Ginekologija in reprodukcija: Genomika za personalizirano medicino

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P4-0220
• Naslov: Primerjalna genomika in genomska biodiverziteta