Background Disease clustering is a growing public health concern and is increasingly linked to adverse socioeconomic conditions. Few population-based studies have focussed on interaction between non-communicable diseases. In this cross-sectional study, we examine clustering of, and synergistic interactions between, frequently occurring non-communicable diseases in Katwijk, a former fishing village in the Netherlands. Additionally, our study identifies contextual variables associated with these clusters of non-communicable diseases. Methods In a survey among adults (>19 years) living in the former fishing village Katwijk, Netherlands, were asked about non-communicable diseases, psychological distress, self-rated health scores and contextual factors, eg, socio-demographic, psychosocial and health behavior characteristics. Interaction was measured on the additive and the multiplicative scale. We used generalized ordered logistic regression analysis to examine associations with contextual variables. Results Three disease clusters were found to be most prevalent among the study participants (n = 1408). Each cluster involved a combination of frequently occurring conditions in this population: psychological distress (n = 261, 19%), cardiometabolic diseases (n = 449, 32%) and musculoskeletal pain (n = 462, 33%). These three diseases interact synergistically on the additive scale to increase the odds of reporting a low self-rated health. None of the disease clusters showed a statistically significant positive interaction on a multiplicative scale. Multiple contextual factors were associated with these disease clusters, including gender, loneliness, experiencing financial stress, and a BMI≥30. Conclusion Our findings imply that psychological distress, cardiometabolic diseases and musculoskeletal pain synergistically interact, leading to a much lower self-rated health than expected. Several contextual factors are related to this interaction emphasizing the importance of a multicomponent, ecological approach
