Genetic predictors of relapse rate in pediatric MS

Multiple Sclerosis : Clinical and Laboratory Research
Jennifer GravesU.S. Network of Pediatric MS Centers

Abstract

Genetic ancestry, sex, and individual alleles have been associated with multiple sclerosis (MS) susceptibility. To determine whether established risk factors for disease onset are associated with relapse rate in pediatric MS. Whole-genome genotyping was performed for 181 MS or high-risk clinically isolated syndrome patients from two pediatric MS centers. Relapses and disease-modifying therapies were recorded as part of continued follow-up. Participants were characterized for 25-hydroxyvitamin D serum status. Ancestral estimates (STRUCTURE v2.3.1), human leukocyte antigen (HLA)-DRB1*15 carrier status (direct sequencing), sex, and a genetic risk score (GRS) of 110 non-HLA susceptibility single-nucleotide polymorphisms (SNPs) were evaluated for association with relapse rate with Cox and negative binomial regression models. Over 622 patient-years, 408 relapses were captured. Girls had greater relapse rate than boys (incident rate ratio (IRR) = 1.40, 95% confidence interval (CI) = 1.04-1.87, p = 0.026). Participants were genetically diverse; ~40% (N = 75) had <50% European ancestry. HLA-DRB1*15 status modified the association of vitamin D status (pixn = 0.022) with relapse rate (per 10 ng/mL, in DRB1*15+ hazard ratio (HR) = 0.72, 95...Continue Reading

References

Apr 17, 2002·Science·Howard M CannL Luca Cavalli-Sforza
Dec 12, 2003·American Journal of Human Genetics·Jorge R OksenbergStephen L Hauser
Apr 18, 2007·Neurology·Lauren B KruppUNKNOWN International Pediatric MS Study Group
Jan 14, 2009·Archives of Neurology·Mark P GormanTanuja Chitnis
Oct 15, 2009·Nature Reviews. Neurology·E Ann YehUNKNOWN US Network of Pediatric Multiple Sclerosis Centers of Excellence
Feb 4, 2011·Neurology·G DisantoUNKNOWN Canadian Pediatric Demyelinating Disease Network
Jun 10, 2011·Genes and Immunity·UNKNOWN International Multiple Sclerosis Genetics Consortium
Aug 13, 2011·Nature·UNKNOWN International Multiple Sclerosis Genetics ConsortiumAlastair Compston
Aug 29, 2012·Annals of Neurology·Ellen M MowryDaniel Pelletier
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Feb 16, 2013·Brain : a Journal of Neurology·Pierre-Antoine GourraudSergio E Baranzini
Jul 28, 2013·Multiple Sclerosis : Clinical and Laboratory Research·Rui LinIngrid van der Mei
Aug 2, 2013·Genes and Immunity·N IsobeP-A Gourraud
Oct 1, 2013·Nature Genetics·UNKNOWN International Multiple Sclerosis Genetics Consortium (IMSGC)Jacob L McCauley
Nov 11, 2014·Annals of Neurology·Dorlan J KimbroughPeter A Calabresi
Jan 27, 2015·Brain : a Journal of Neurology·An GorisHanne F Harbo
May 4, 2015·BMC Neurology·Richard S NicholasDaniel M Altmann
May 8, 2015·Multiple Sclerosis : Clinical and Laboratory Research·Kelly HilvenAn Goris

❮ Previous
Next ❯

Citations

May 14, 2019·Multiple Sclerosis : Clinical and Laboratory Research·Jennifer S GravesEmmanuelle Waubant
Jul 26, 2017·Journal of Neurology, Neurosurgery, and Psychiatry·Yuan ZhouUNKNOWN Ausimmmune/AusLong investigators group
Jul 26, 2017·Expert Review of Clinical Immunology·Eliza Gordon-Lipkin, Brenda Banwell
Mar 7, 2020·Multiple Sclerosis Journal - Experimental, Translational and Clinical·Maria GontikaMaria Anagnostouli
Apr 25, 2018·Current Treatment Options in Neurology·Vilija G JokubaitisBruce V Taylor
Feb 8, 2018·Multiple Sclerosis and Related Disorders·Jennifer S GravesIngrid A F van der Mei
May 18, 2021·Paediatric Drugs·Cristina Fernandez-CarbonellLauren B Krupp
Sep 9, 2021·Expert Review of Neurotherapeutics·Amin ZarghamiBruce V Taylor

❮ Previous
Next ❯

Methods Mentioned

BETA
genetic modification

Software Mentioned

Illumina GenomeStudio
PLINK
STRUCTURE
IMPUTE2
ShapeIT

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.