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Irritable bowel syndrome (IBS) clusters in families, but previous studies documented family history only from patients. We have shown that patient–relative agreement on IBS status is poor. Thus, we conducted a family case–control study with direct survey of symptoms from family members to better quantitate the aggregation of IBS in families. The aims of this study were to (i) compare the prevalence of IBS in case-relatives with control-relatives, and (ii) determine whether gender, relationship, predominant symptom, and environmental risk factors affect familial aggregation.Outpatients with IBS, matched controls, and their first-degree relatives completed a bowel symptom questionnaire. Percent of cases and controls with a family history were compared and odds ratios were computed usingχ2-test; recurrence risks to relatives were computed using logistic regression and generalized estimating equations.Data were collected from 477 cases, 297 controls, 1,492 case-relatives, and 936 control-relatives. Probands had a median age of 50 and 78% were women. 50% of case and 27% of control families had at least another relative with IBS yielding an odds ratio of 2.75 (95% CI: 2.01–3.76,P<0.0001). When aggregation estimates were reevaluated stratifying by relative relationship or proband gender, generational and gender effects were not observed. Familial clustering by bowel habit was weakest for diarrhea, and strongest for alternating bowel habits.IBS aggregates strongly in families. The strength of the association does vary somewhat by relationship to proband, but the lack of association in spouses supports either a possible genetic etiology or a shared household environmental exposure as an underlying cause of IBS.