Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ∼8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (Pcomb<5×10−8): NCF2 (Pcomb = 2.87×10−11), IKZF1 (Pcomb = 2.33×10−9), IRF8 (Pcomb = 1.24×10−8), IFIH1 (Pcomb = 1.63×10−8), and TYK2 (Pcomb = 3.88×10−8). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to ∼30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

The Grizzly, February 24, 2005

Spring Break Closing Information • Board of Trustees Meet to Discuss Issues on Campus • Fundraising Facts: Numbers Increase for Airband and Tsunami Relief Effort • Negro Spirituals Celebrate Black History Month • The Face in the Mirror: A Groundbreaking New Play for Ursinus • Competing Condoms: Consumer Reports Rates the Efficacy of Various Brands • Opinions: On the Look-out for a Boat Anchor?; Does UC Give Enough Charitable Support? • Wrestlers Grapple Conferences and Nationals • Bears Clinch Playoff Berthhttps://digitalcommons.ursinus.edu/grizzlynews/1579/thumbnail.jp

The Grizzly, April 14, 2005

Iraqi Visit for Model UN • Airband Raises Over $12k for Charity • Spring Fling is in the Air • Death of the Pope • UC\u27s Five Year Plan • Collective Soul Concert a Success • Ritter\u27s Last Play Debuts • Business Students go All-in for ALS • Art of Emotional Foreplay • Who\u27s in the Accepted Class of 2009? • Opinions: Lesson in Filibustering: Why You Need to Know; It\u27s my Party, I Invite Who I Want to; It\u27s the Most Wonderful Time of the Year; People Don\u27t Cause Traffic Problems, SUVs Do • Long Week for Women\u27s Softball • Women\u27s Lacrosse Team Continues Winning Streakhttps://digitalcommons.ursinus.edu/grizzlynews/1583/thumbnail.jp

Analysis of Ground Ambulance Crash Data From 2012 to 2018

DTNH2216D00011, 693JJ919F000191This study reviewed ground ambulance crashes that occurred from 2012 to 2018 in the United States. The study queried several national crash databases and reviewed NHTSA\u2019s Special Crash Investigation reports for ambulance-involved crashes. The objective of the study was to review ambulance crashes that occurred from 2012 to 2018 to identify factors contributing to ambulance-involved crashes and injuries and identify priority countermeasures to increase ambulance safety. Findings suggest several priority countermeasures to improve ground ambulance safety: (1) Strengthen organizational safety polices; (2) Reduce operator error through training; (3) Create a culture of safety; and (4) Adopt new vehicle safety designs or technologie

The Grizzly, April 21, 2005

A Taste of Asia • Students Raise Over $3,000 for Multiple Sclerosis • U.S.-Israeli Relations: On Cold Terms? • Why Kaleidoscope? • Class Elections: Who Will Get Your Vote? • Talent Show this Friday • Ursinus Students Take a Vow of Silence • New Mugs in Zack\u27s Promote Environmental Awareness • Our Town Makes its Mark as Ritter\u27s Last Play • Spread Your Legs and Turn Your Head and Cough • Opinions: Academic Honor Code: Is it Really Necessary?; Scope the Opening ; Questions that Need to be Considered by the Ursinus Campus • Men\u27s Baseball: Trying to Make a Push for the Playoffs • Conference Woes Continue for Men\u27s Lacrosse • A Struggling Season Shows Some Signs of Improvement for Tennis Teamshttps://digitalcommons.ursinus.edu/grizzlynews/1584/thumbnail.jp

Influence of caregiver network support and caregiver psychopathology on child mental health need and service use in the LONGSCAN study

Using structural equation modeling, this study examined the relationship of caregiver network support on caregiver and child mental health need, as well as child mental health service use among 1075 8-year-old children participating in the LONGSCAN study. The final model showed acceptable fit (χ2 = 301.476, df = 136, p<0.001; RMSEA = 0.052; CFI = 0.95). Caregiver and child mental health needs were positively related. As predicted, caregiver network support exerted a protective effect, with greater levels of caregiver network support predictive of lower caregiver and child need. Contrary to prediction, however, caregiver network support was not directly related to child service use. Higher child need was directly related to child service use, especially among children whose caregivers had mental health problems. The findings appear to indicate that lower levels of caregiver network support may exert its impact on child service use indirectly by increasing caregiver and child need, rather than by directly increasing the likelihood of receiving services, especially for African American children

Risk Alleles for Systemic Lupus Erythematosus in a Large Case-Control Collection and Associations with Clinical Subphenotypes

Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. Recent studies have greatly expanded the number of established SLE risk alleles, but the distribution of multiple risk alleles in cases versus controls and their relationship to subphenotypes have not been studied. We studied 22 SLE susceptibility polymorphisms with previous genome-wide evidence of association (p<5×10−8) in 1919 SLE cases from 9 independent Caucasian SLE case series and 4813 independent controls. The mean number of risk alleles in cases was 15.1 (SD 3.1) while the mean in controls was 13.1 (SD 2.8), with trend p = 4×10−128. We defined a genetic risk score (GRS) for SLE as the number of risk alleles with each weighted by the SLE risk odds ratio (OR). The OR for high-low GRS tertiles, adjusted for intra-European ancestry, sex, and parent study, was 4.4 (95% CI 3.8–5.1). We studied associations of individual SNPs and the GRS with clinical manifestations for the cases: age at diagnosis, the 11 American College of Rheumatology classification criteria, and double-stranded DNA antibody (anti-dsDNA) production. Six subphenotypes were significantly associated with the GRS, most notably anti-dsDNA (ORhigh-low = 2.36, p = 9e−9), the immunologic criterion (ORhigh-low = 2.23, p = 3e−7), and age at diagnosis (ORhigh-low = 1.45, p = 0.0060). Finally, we developed a subphenotype-specific GRS (sub-GRS) for each phenotype with more power to detect cumulative genetic associations. The sub-GRS was more strongly associated than any single SNP effect for 5 subphenotypes (the above plus hematologic disorder and oral ulcers), while single loci are more significantly associated with renal disease (HLA-DRB1, OR = 1.37, 95% CI 1.14–1.64) and arthritis (ITGAM, OR = 0.72, 95% CI 0.59–0.88). We did not observe significant associations for other subphenotypes, for individual loci or the sub-GRS. Thus our analysis categorizes SLE subphenotypes into three groups: those having cumulative, single, and no known genetic association with respect to the currently established SLE risk loci