Characteristics of the Co-Morbidity of Irritable Bowel Syndrome: A Secondary Analysis of Existing Twin Data

Irritable bowel syndrome (IBS) is a chronic disorder whose manifestations typically fluctuate over time. Prior epidemiologic studies estimate the one-year prevalence as 7-20%, depending on criteria used to define IBS. Individuals with IBS demonstrate a high co-occurrence with common functional somatic syndromes and psychiatric disorders; however, the majority of these associations derive from non-population-based studies. We examined associations between IBS risk factors and Rome II-defined IBS in a U.S. population-based twin registry. Data from 4,591 male and female twins were available for this analysis. Variables representing self-reported presence of IBS, major depressive disorder (MDD), chronic widespread pain (CWP), fatiguing illness (CFS-like illness), Medical Outcomes Study short form (SF-12) scores and other personal characteristics were obtained through questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated as measures of association between IBS risk factors and IBS. The prevalence of lifetime IBS was 4.7% (95% CI: 4.1, 5.4). Positive associations were observed between IBS and lifetime MDD (OR=2.0, 95% CI: 1.5, 2.7), lifetime CWP (OR=3.9, 95% CI: 2.7, 5.5), lifetime CFS-like illness (OR=4.7, 95% CI: 3.0, 7.3), and female sex (OR=2.0, 95% CI: 1.4, 2.8). Age, body size, and SF-12 scores demonstrated approximately null associations with IBS. We further examined the overlap of individuals with IBS and MDD since both disorders suggest a familial tendency and demonstrate a higher than expected co-occurrence. Using the population-based Swedish Twin Registry, we examined the genetic and environmental architecture of the co-occurrence of IBS and MDD among 31,407 twins who contributed information on medical data and personal characteristics via phone interview. Both the case-control study and the co-twin control study design demonstrated an increased association between MDD and IBS (OR=2.7, 95% CI: 2.3, 3.2), and (OR=2.2, 95% CI, 1.5, 3.2), respectively. Thus, genetic and environmental factors did not confound the association between MDD and IBS; rather one of these disorders may predispose individuals to the other disorder. The positive associations observed between MDD and IBS suggest a possible hypothesis whereby one disorder is part of the causal disease mechanism of the other disorder, thereby leading to a high co-occurrence between MDD and IBS

Prevalence of clinically actionable disease variants in exceptionally long-lived families

BACKGROUND: Phenotypic expression of pathogenic variants in individuals with no family history of inherited disorders remains unclear. METHODS: We evaluated the prevalence of pathogenic variants in 25 genes associated with Mendelian-inherited disorders in 3015 participants from 485 families in the Long Life Family Study (LLFS). Boot-strapping and Fisher\u27s exact test were used to determine whether allele frequencies in LLFS were significantly different from the allele frequencies reported in publicly available genomic databases. RESULTS: The proportions of pathogenic autosomal dominant mutation carriers in BRCA1 and SDHC in LLFS study participants were similar to those reported in publicly available genomic databases (0.03% vs. 0.0008%, p = 1 for BRCA1, and 0.08% vs. 0.003%, p = 0.05 for SDHC). The frequency of carriers of pathogenic autosomal recessive variants in CPT2, ACADM, SUMF1, WRN, ATM, and ACADVL were also similar in LLFS as compared to those reported in genomic databases. The lack of clinical disease among LLFS participants with well-established pathogenic variants in BRCA1 and SDHC suggests that penetrance of pathogenic variants may be different in long lived families. CONCLUSION: Further research is needed to better understand the penetrance of pathogenic variants before expanding large scale genomic testing to asymptomatic individuals