Cindy Boer

General Introduction | 25 1.1 has been well-documented[59, 60]. Individuals with high BMI (body mass Index) have a significantly different microbiome than those who are not obese.Obesity is one of the most well-known and characterized risk factor for osteoarthritis [61, 62]. The increased risk for osteoarthritis is thought to be due to increased loading of the joint. Howev- er, this would not explain the observed increased risk for osteoarthritis in non-weight bearing joints, such as the hands[63]. Another explanation is the increased systemic inflammation seen in obese individuals[64], which is thought to arise due to the differ- ences/dysbiosis in the microbiome of obese individuals[65]. Postulated is that changes in the gut microbiome due to the environment (obesity) can lead to an increased sys- temic inflammatory state (low grade inflammation)[55]. This is something that will be explored in Chapter 5 . Osteoarthritis In the Rotterdam Study All of the studies in this thesis were performed with the use of the “Rotterdam Study” co- horts, also known in Dutch as the “Erasmus Rotterdam Gezondheid Onderzoek”(ERGO) [66] . This is a population-based prospective cohort, designed to study the determinants of aging. The Rotterdam Study consists of several sub-cohorts ( Figure 7 ) , all consisting of individuals (>45 years of age) living in the well-defined suburb of Ommoord in the city of Rotterdam, the Netherlands. Participants were examined in detail at baseline in 1990 via home interviews and an extensive set of examinations at the specifically built research enterer in Ommoord. In addition, follow-up examinations were repeated every 3-4 years. The Rotterdam Study focusses on 14 different research lines in the context of “healthy aging” which includes all major organ systems and related diseases and , important for the studies described in this thesis, also diseases of the musculoskeletal system such as osteoporosis and osteoarthritis, In addition, many important determi- nants of disease are documented and studied including, e.g., medication use, dietary patterns, and genetics and genomics. Also extensive bio-banking is part of this long running cohort study, in particular blood is collected at each follow-up measurement fromwhich DNA was extracted. The DNA has been subjected to several genetic analyses, most notably a large SNP array genotyping effort, to allow GWAS studies taking place with all the data in RS, which started in 2008 and has since been extended to include al- most the complete cohort. Relevant for OA research, radiographs were made of multiple joints, such as knees, hips and hands at baseline and during follow-up examinations. All radiographs have been scored on the Kellgren-Lawrence osteoarthritis severity scoring by expert clinicians.