دورية أكاديمية
Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation
| العنوان: | Investigating the role of common and rare variants in multiplex multiple sclerosis families reveals an increased burden of common risk variation |
|---|---|
| المؤلفون: | Elif Everest, Mohammad Ahangari, Ugur Uygunoglu, Melih Tutuncu, Alper Bulbul, Sabahattin Saip, Taskin Duman, Ugur Sezerman, Daniel S. Reich, Brien P. Riley, Aksel Siva, Eda Tahir Turanli |
| المصدر: | Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022) |
| بيانات النشر: | Nature Portfolio, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a significantly higher common risk variation burden compared with population controls and control families. Sporadic MS cases tended to have a higher PRS compared with familial MS cases, suggesting the presence of a higher rare risk variation burden in the families. In line with this, score distributions among affected and unaffected family members within individual families showed that known susceptibility alleles can explain disease development in some high-risk multiplex families, while in others, additional genetic contributors increase MS risk. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-022-21484-x |
| الوصول الحر: | https://doaj.org/article/7acd82bda4b04a91b990b573b6ebbd1eTest |
| رقم الانضمام: | edsdoj.7acd82bda4b04a91b990b573b6ebbd1e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
|---|---|
| DOI: | 10.1038/s41598-022-21484-x |