The potential of online social networking data for augmenting the study of high-risk personal networks among young men who have sex with men at-risk for HIV.

Capturing dynamics in high-risk personal networks is essential for preventing HIV transmission. Online social networking data offer incentive to augment traditional selfreported approaches for network enumeration. To explore what online networks reveal about dynamics among high-risk associates, we examine the relationship between egocentric confidant and sex networks and personal Facebook friendship networks of a cohort of young Black men who have sex with men. Although overlap exists between self-reported and Facebook associates, the stabilities of each were unrelated. Confidants who were also Facebook friends with a respondent were, however, more likely to be retained. Thus, Facebook networks contain stable confidants.

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF.

BACKGROUND & AIMS: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor ß common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared. RESULTS: In the discovery cohort, we associated CD with a frameshift mutation in CSF2RB (P = 8.52 × 10(-4)); the finding was validated in the replication cohort (combined P = 3.42 × 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected with full-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) had reduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. CONCLUSIONS: In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.

Air pollution exposure is associated with rhinitis in older US adults via specific immune mechanisms.

BACKGROUND: Pathophysiology of rhinitis in older adults is largely unknown. We tested whether air pollution is associated with this condition and how immune mechanisms may play a role in this relationship. METHODS: We analyzed cross-sectional data from the National Social Life, Health, and Aging Project, a nationally representative study of older adults born between 1920 and 1947. Particulate matter ≤2.5 µm (PM2.5 ) air pollution exposure estimates were generated using validated spatiotemporal models. Presence of rhinitis was defined based on medication use (≥1: intranasal medications: steroids, antihistamines, lubricants, and/or decongestants, and/or oral medications: antihistamines and/or decongestants). K-means cluster analysis (Jaccard method) was used to group 13 peripheral blood cytokines into 3 clusters to facilitate functional determination. We fitted multivariate logistic regressions to correlate PM2.5 exposure with presence of rhinitis, controlling for confounders, and then determined the role of cytokines in this relationship. RESULTS: Long- (but not short-) term exposure to PM2.5 was associated with presence of rhinitis: 3-year exposure window, odds ratio (OR) = 1.32, 95% confidence interval (CI): 0.98, 1.80, per 1 standard deviation (SD) PM2.5 increase. Inclusion of cytokine cluster in the model led to a modestly stronger effect of PM2.5 exposure on rhinitis (OR = 1.37; 95% CI: 1.00, 1.87; 3-year exposure window). The particular immune profile responsible for this result was composed of elevated IL-3, IL-12, and IFN-γ (OR = 4.86, 95% CI: 1.10, 21.58, immune profile-PM2.5 exposure interaction term). CONCLUSION: We show for the first time that IL-3, IL-12, and IFN-γ explain in part the relationship between PM2.5 exposure and rhinitis in older US adults. If confirmed, these immune pathways may be used as therapeutic targets.

Prediabetes Progression and Reversion: Social Factors and Racial/Ethnic Differences.

OBJECTIVE: Racial and ethnic minorities are disproportionately affected by diabetes. Social characteristics, such as family structure, social support, and loneliness, may contribute to these health disparities. In a nationally representative sample of diverse older adults, we evaluated longitudinal rates of both progression from prediabetes to diabetes and reversion from prediabetes to normoglycemia. RESEARCH DESIGN AND METHODS: Using the longitudinal Health and Retirement Study (2006-2014), our sample included 2625 follow-up intervals with a prediabetes baseline (provided by 2229 individuals). We analyzed 4-year progression and reversion rates using HbA1c and reported presence or absence of physician-diagnosed diabetes. We utilized chi-square and logistic regression models to determine how race/ethnicity and social variables influenced progression or reversion controlling for comorbidities and demographics. RESULTS: Overall, progression to diabetes was less common than reversion (17% vs. 36%). Compared to Whites, Hispanic/Latino respondents had higher odds of progression to diabetes from prediabetes while Black respondents had lower odds of reversion, adjusting for physical health and demographics. For social variables, Hispanics/Latinos had the highest reliance on and openness with family and the lowest rates of loneliness. The inclusion of social variables in regression models reduced the odds of progression for Hispanics/Latinos but did not alter Black's lower rate of reversion. CONCLUSIONS: Hispanic/Latinos and Blacks not only had different transition pathways leading to diabetes, but also had different social profiles, affecting Hispanic/Latino progression, but not Black reversion. These differences in the influence of social variables on diabetes risk may inform the design of culturally-specific efforts to reduce disparities in diabetes burden.

Genome-wide association identifies multiple ulcerative colitis susceptibility loci.

Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10(-5). Seven of these loci exceeded genome-wide significance (P < 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.