Background Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway genes lead to a class of disorders known as RASopathies, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and autism spectrum disorders (ASD). Although the literature offers conflicting evidence for association of NF1 and autism, there has been no systematic evaluation of autism traits in the RASopathies as a class to support a role for germline Ras/MAPK activation in ASDs. Methods We examined the association of autism traits with NF1, NS, CS and CFC, comparing affected probands with unaffected sibling controls and subjects with idiopathic ASDs using the qualitative Social Communication Questionnaire (SCQ) and the quantitative Social Responsiveness Scale (SRS). Results Each of the four major RASopathies showed evidence for increased qualitative and quantitative autism traits compared with sibling controls. Further, each RASopathy exhibited a distinct distribution of quantitative social impairment. Levels of social responsiveness show some evidence of correlation between sibling pairs, and autism-like impairment showed a male bias similar to idiopathic ASDs. Conclusions Higher prevalence and severity of autism traits in RASopathies compared to unaffected siblings suggests that dysregulation of Ras/MAPK signalling during development may be implicated in ASD risk. Evidence for sex bias and potential sibling correlation suggests that autism traits in the RASopathies share characteristics with autism traits in the general population and clinical ASD population and can shed light on idiopathic ASDs.

American Muslims have low rates of mammography utilization, and research suggests that religious values influence their health-seeking behaviors. We assessed associations between religion-related factors and breast cancer screening in this population. A diverse group of Muslim women were recruited from mosques and Muslim organization sites in Greater Chicago to self-administer a survey incorporating measures of fatalism, religiosity, discrimination, and Islamic modesty. 254 surveys were collected of which 240 met age inclusion criteria (40 years of age or older). Of the 240, 72 respondents were Arab, 71 South Asian, 59 African American, and 38 identified with another ethnicity. 77 % of respondents had at least one mammogram in their lifetime, yet 37 % had not obtained mammography within the past 2 years. In multivariate models, positive religious coping, and perceived religious discrimination in healthcare were negatively associated with having a mammogram in the past 2 years, while having a PCP was positively associated. Ever having a mammogram was positively associated with increasing age and years of US residency, and knowing someone with breast cancer. Promoting biennial mammography among American Muslims may require addressing ideas about religious coping and combating perceived religious discrimination through tailored interventions.

Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Potential genetically encoded sex differences we investigated include differential genetic liability thresholds or distributions, gene-sex interaction at autosomal loci, major contribution of the X-chromosome, or gene-environment interactions reflected in genes responsive to androgens or estrogens. Finally, we tested the overlap between sex-differential association with anthropometric traits and disease risk. We utilized complementary approaches of assessing GWAS association enrichment and SNP-based heritability estimation to explore explicit sex differences, as well as enrichment in sex-implicated functional categories. We do not find consistent increased genetic load in the lower-prevalence sex, or a disproportionate role for the X-chromosome in disease risk, despite sex-heterogeneity on the X for several traits. We find that all anthropometric traits show less than complete correlation between the genetic contribution to males and females, and find a convincing example of autosome-wide genome-sex interaction in multiple sclerosis (P = 1 × 10). We also find some evidence for hormone-responsive gene enrichment, and striking evidence of the contribution of sex-differential anthropometric associations to common disease risk, implying that general mechanisms of sexual dimorphism determining secondary sex characteristics have shared effects on disease risk.

Background: The limited research of breast cancer screening among different American Muslim groups consistently demonstrates low rates of mammography. There has been no survey of how religion-related factors influence screening patterns in a diverse sample of American Muslims. Methods: We partnered with the Council of Islamic Organizations of Greater Chicago to survey English-speaking women aged 40 years and older frequenting mosques and community sites. The self-administered survey included several adapted measures of religiosity, fatalism, and discrimination from the literature, and incorporated a pilot measure of Islamic modesty. Results: 240 women completed the survey with nearly equal numbers of indigenous African Americans (27%), Arab Americans (33%), and South Asians (32%). 77% of the sample reported ever having a mammogram while only 37% had a mammogram within the past 1-2 years. There were no significant differences in rates by race/ethnicity. On multivariate analysis positive religious coping (OR= 0.21, p <0.05) and perceived religious identity-directed discrimination (OR=0.74, p<0.05) were negatively associated with having biennial mammograms, while having a primary care physician (OR=20, p<0.01,) greatly increased the odds of having a mammogram. Ever having a mammogram was positively associated with years of US residence (>20 yrs OR=4.3, p<0.05) and increasing level of educational attainment. Islamic modesty, fatalistic beliefs, breast cancer knowledge, educational attainment, insurance status and were not associated with mammography rates. Conclusions: Cancer disparity research typically focuses on inequities across ethnic and racial lines, and therefore overlooks the influence of a shared religion upon health behaviors across race and ethnicity. Our survey suggests that religion-related factors such as positive religious coping and perceived religious discrimination influence breast cancer screening patterns among American Muslims. Consequently, programs leveraging shared religious networks, such as mosques and Imams, may be a means to address religious barriers that impede screening across ethnic and racial lines. Citation Format: Aasim I. Padela, Sohad Murrar, Brigid Adviento, Zahra Hosseinain, Monica Peek, Olufunmilayo Olopade, Farr Curline. Associations between religion-related factors and breast cancer screening among American Muslims. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C52. doi:10.1158/1538-7755.DISP13-C52

The PREMM5 model is a web-based clinical prediction algorithm that estimates the gene-specific risk of an individual carrying a Lynch syndrome germline mutation based on targeted family history questions. The objectives of our study were to determine the feasibility of screening for LS in an urban, minority patient population in a primary care setting using the PREMM5 model and characterize patient barriers associated with difficulty completing the questions. Participants were recruited from Tulane Internal Medicine primary care clinics on 9 random collection dates. Our data illustrates the difficulty patients have in recalling important details necessary to answer the PREMM questionnaire.