scholarly journals Burden of genetic risk variants in multiple sclerosis families in the Netherlands

2016 ◽  
Vol 2 ◽  
pp. 205521731664872 ◽  
Author(s):  
Julia Y Mescheriakova ◽  
Linda Broer ◽  
Simin Wahedi ◽  
André G Uitterlinden ◽  
Cornelia M van Duijn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Weighted Genetic Risk Score ◽  
Sporadic Cases ◽  
Multiplex Families ◽  
The Difference ◽  
Multiple Sclerosis Patients ◽  
Genetic Burden

Background Approximately 20% of multiple sclerosis patients have a family history of multiple sclerosis. Studies of multiple sclerosis aggregation in families are inconclusive. Objective To investigate the genetic burden based on currently discovered genetic variants for multiple sclerosis risk in patients from Dutch multiple sclerosis multiplex families versus sporadic multiple sclerosis cases, and to study its influence on clinical phenotype and disease prediction. Methods Our study population consisted of 283 sporadic multiple sclerosis cases, 169 probands from multiplex families and 2028 controls. A weighted genetic risk score based on 102 non-human leukocyte antigen loci and HLA-DRB1*1501 was calculated. Results The weighted genetic risk score based on all loci was significantly higher in familial than in sporadic cases. The HLA-DRB1*1501 contributed significantly to the difference in genetic burden between the groups. A high weighted genetic risk score was significantly associated with a low age of disease onset in all multiple sclerosis patients, but not in the familial cases separately. The genetic risk score was significantly but modestly better in discriminating familial versus sporadic multiple sclerosis from controls. Conclusion Familial multiple sclerosis patients are more loaded with the common genetic variants than sporadic cases. The difference is mainly driven by HLA-DRB1*1501. The predictive capacity of genetic loci is poor and unlikely to be useful in clinical settings.

Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis

2014 ◽  
Vol 21 (11) ◽  
pp. 1463-1467 ◽  
Author(s):  
Melissa Sorosina ◽  
Federica Esposito ◽  
Clara Guaschino ◽  
Ferdinando Clarelli ◽  
Nadia Barizzone ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Age At Onset ◽  
Inverse Correlation ◽  
Inflammatory Phase ◽  
Risk Variants ◽  
Weighted Genetic Risk Score

We correlated the weighted genetic risk score measured using 107 established susceptibility variants for multiple sclerosis (MS) with the age at onset in bout-onset (BOMS, n=906) and progressive-onset MS Italian patients (PrMS) ( n=544). We observed an opposite relationship in the two disease courses: a higher weighted genetic risk score was associated with an earlier age at onset in BOMS (rho= −0.1; p=5 × 10−3) and a later age at onset in PrMS cases (rho=0.07; p=0.15) ( p of difference of regression=1.4 × 10−2). These findings suggest that established MS risk variants anticipate the onset of the inflammatory phase, while they have no impact on, or even delay, the onset of the progressive phase.

scholarly journals A Weighted Genetic Risk Score Predicts Surgical Recurrence Independent of High-Risk Clinical Features in Dupuytren’s Disease

2019 ◽  
Vol 143 (2) ◽  
pp. 512-518 ◽  
Author(s):  
Sophie A. Riesmeijer ◽  
Oliver W. G. Manley ◽  
Michael Ng ◽  
Ilja M. Nolte ◽  
Dieuwke C. Broekstra ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Features ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Dupuytren’S Disease ◽  
Dupuytren's Disease ◽  
Surgical Recurrence ◽  
Weighted Genetic Risk Score

scholarly journals Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
Ahmed El‐Boraie ◽  
Taraneh Taghavi ◽  
Meghan J. Chenoweth ◽  
Koya Fukunaga ◽  
Taisei Mushiroda ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Weighted Genetic Risk Score

scholarly journals Pregnancy does not modify the risk of MS in genetically susceptible women

2020 ◽  
Vol 7 (6) ◽  
pp. e898
Author(s):  
Cameron J. Adams ◽  
Sean L. Wu ◽  
Xiaorong Shao ◽  
Patrick T. Bradshaw ◽  
Edlin Gonzales ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
The United States ◽  
Sensitivity Analyses ◽  
Risk Variants ◽  
Inverse Variance ◽  
Weighted Genetic Risk Score ◽  
Meta Analyses ◽  
Genetic Risk Variants

ObjectiveTo use the case-only gene-environment (G E) interaction study design to estimate interaction between pregnancy before onset of MS symptoms and established genetic risk factors for MS among White adult females.MethodsWe studied 2,497 female MS cases from 4 cohorts in the United States, Sweden, and Norway with clinical, reproductive, and genetic data. Pregnancy exposure was defined in 2 ways: (1) live birth pregnancy before onset of MS symptoms and (2) parity before onset of MS symptoms. We estimated interaction between pregnancy exposure and established genetic risk variants, including a weighted genetic risk score and both HLA and non-HLA variants, using logistic regression and proportional odds regression within each cohort. Within-cohort associations were combined using inverse variance meta-analyses with random effects. The case-only G × E independence assumption was tested in 7,067 individuals without MS.ResultsEvidence for interaction between pregnancy exposure and established genetic risk variants, including the strongly associated HLA-DRB1*15:01 allele and a weighted genetic risk score, was not observed. Results from sensitivity analyses were consistent with observed results.ConclusionOur findings indicate that pregnancy before symptom onset does not modify the risk of MS in genetically susceptible White females.

THU0010 A Weighted Genetic Risk Score Using 46 Loci to Predict Rheumatoid Arthritis Risk

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A167.3-A168 ◽  
Author(s):  
A. Yarwood ◽  
M. Lunt ◽  
B. Han ◽  
S. Raychaudhuri ◽  
J. Bowes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Rheumatoid Arthritis Risk ◽  
Weighted Genetic Risk Score

scholarly journals Alzheimer’s Genetic Risk Score linked to Incident Mild Behavioral Impairment

2017 ◽  
Author(s):  
Shea J. Andrews ◽  
Zahinoor Ismail ◽  
Kaarin J. Anstey ◽  
Moyra Mortby
Keyword(s):  
Cognitive Impairment ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
Neuropsychiatric Symptoms ◽  
Later Life ◽  
Behavioral Impairment ◽  
Affective Dysregulation ◽  
Weighted Genetic Risk Score ◽  
Shared Risk

AbstractMild Behavioral Impairment (MBI) describes the emergence of later-life Neuropsychiatric Symptoms (NPS) as an at-risk state for cognitive decline and dementia and as a potential manifestation of prodromal dementia. How NPS mechanistically link to the development of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) is not fully understood. Potential mechanisms include either shared risk factors that are related to both NPS and cognitive impairment, or AD pathology promoting NPS. This is the first study to examine whether AD genetic loci, individually and as a genetic risk score, are a shared risk factor with MBI. 1377 older adults (aged 72-79; 738 males; 763 normal cognition) from the PATH Through Life project. MBI was assessed in accordance with Criterion 1 of the ISTAART-AA diagnostic criteria using the Neuropsychiatric Inventory. 25 LOAD risk loci were genotyped and a weighted genetic risk score (GRS) was constructed. Binomial logistic regression adjusting for age, gender, and education examined the association between LOAD GRS and MBI domains. An increase in the LOAD GRS and APOE*ε4 were associated with higher likelihood of Affective Dysregulation;MS4A4A-rs4938933*C andMS4A6A-rs610932*G were associated with a reduced likelihood of Affective Dysregulation;ZCWPW1-rs1476679*C was associated with a reduced likelihood of Social Inappropriateness and Abnormal Perception;BIN1-rs744373*G andEPHA1-rs11767557*C were associated with higher likelihood of Abnormal Perception;NME8-rs2718058*G was associated with a reduced likelihood Decreased Motivation. These findings suggest a common genetic etiology between MBI and traditionally recognized memory problems observed in AD and improve our understanding of the pathophysiological features underlying MBI.

scholarly journals Genetic risk factors for pediatric-onset multiple sclerosis

2017 ◽  
Vol 24 (14) ◽  
pp. 1825-1834 ◽  
Author(s):  
Milena A Gianfrancesco ◽  
Pernilla Stridh ◽  
Xiaorong Shao ◽  
Brooke Rhead ◽  
Jennifer S Graves ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Genetic Risk Score ◽  
The United States ◽  
Individual Risk ◽  
Class Iii ◽  
Risk Variants ◽  
Weighted Genetic Risk Score ◽  
Meta Analyses ◽  
Pediatric Onset

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. Methods: Cases with onset <18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases ( n = 7588). Results: HLA–DRB1*15:01 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10−16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated ( p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval: 2.33, 3.32, p < 2.0 × 10−16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA–DRB1*15:01 and HLA–A*02. Conclusion: Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA–DRB1*15:01 and HLA–A*02 are also associated with POMS.

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