Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Increased Burden of Susceptibility Variants in Familial Multiple Sclerosis
Multiple Sclerosis
P16 - Poster Session 16 (5:30 PM-6:30 PM)
9-009
The aim of the study was to reveal underlying genetic factors in multiply affected multiple sclerosis (MS) families.
We previously showed that 7 MS families with 3-to-5 patients and multiple parental consanguinities do not segregate rare, homozygous, complete-penetrance, disease-causing variants. We further explored the underlying reason for the increased MS risk in the studied families by polygenic risk score (PRS) calculations.
A total of 41 individuals in 7 MS families (24 affected, 17 unaffected) and 63 individuals in 19 non-MS control families were included in the study. Family-based phasing was performed using SNP genotypes (710K/2.5M, Illumina) and each chromosome was imputed using the 1000 Genomes Project panel by Beagle 4.0. We determined the genotypes of 232 MS-associated variants resulted from the International MS Genetics Consortium (IMSGC) meta-analysis. SNPs with AR2>0.3 or another SNP with high linkage disequilibrium (r2>0.7) were included in the weighted PRS calculation (173 non-MHC, 16 MHC variants). Mean PRS values were compared between the groups by a one-tail t-test.
MS families had significantly higher mean PRS compared with control families (18.77 vs 17.86, P<0.0001). The difference between MS families and control families remained significant when we excluded HLA-DRB1*1501-alone and all 16 MHC alleles from the analysis (P=0.0002 and P=0.0024, respectively). Affected individuals within MS families also had higher PRS compared with their healthy relatives (19.14 vs 18.26, P=0.01). However, we also observed inter-familial discrepancies.
MS genetic burden is higher in the studied MS families which may explain disease development in some families but not in others. Additional genetic risk factors require to be revealed in families with the observed inconsistency.
Authors/Disclosures
Elif Everest, PhD (National Institutes of Health)
PRESENTER 		Ms. Everest has received personal compensation in the range of $50,000-$99,999 for serving as a postdoctoral visiting fellow with National Institutes of Health.
Ugur Uygunoglu (Cerrahpasa) Ugur Uygunoglu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Turkey . The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen Idec/Gen Pharma of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck-Serono of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanovel of Turkey. The institution of Ugur Uygunoglu has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Genveon of Turkey.
Melih Tutuncu, MD No disclosure on file
Sabahattin Saip Sabahattin Saip has nothing to disclose.
Taskin Duman (Flukara Numune Hospital) Dr. Duman has nothing to disclose.
No disclosure on file
Aksel Siva, MD (Istanbul University Cerrahpasa School of Medicine) Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ali Raif Pharmaceuticals, Turkiye. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanovel Pharmaceuticals, Turkiye. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abdi Ibrahim Ilac - TR. Dr. Siva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono . The institution of Dr. Siva has received research support from Turkish MS Society. The institution of Dr. Siva has received research support from The Scientific and Technological Research Council Of Turkey - Health Sciences Research Grants.
Eda Turanli The institution of Eda Turanli has received research support from Scientific and Technological Research Council of Turkey (TÜBITAK). The institution of Eda Turanli has received research support from Turkish MS Society. The institution of Eda Turanli has received research support from Acibadem University Scientific Research Projects Commission . The institution of Eda Turanli has received research support from Istanbul University Scientific Research Projects Commission .