Cindy Boer

26 | Chapter 1.1 ▲ Figure 7: Overview of the Rotterdam Study. The four Rotterdam Study (RS) cohorts are indicated, and their start and follow-up visits.The Rotterdam Study started in 1990 and is currently still ongoing. Boxes indicate the number of participants for each cohort and visit. RS-I-1 is the largest cohort, and it’s box size functions as reference for the other box sizes. Data used in this thesis: X-ray data was available for RS-I-1, RS-1-2, RS-1-4, RS-II-1, RS-II-2, RS-III-1 and RS-III-2. Microbiome and pain data was available for RS-III-2. Pharmacological data was avalible for RS-I, and RS-II. Outline and aim of this thesis The aim of this thesis is to identify novel genes involved in the pathogenesis of osteo- arthritis, in order to gain greater insight into the pathology of osteoarthritis and bring possible preventive or curative treatments closer for one of the world’s oldest diseases. In Chapter 2 , osteoarthritis endophenotypes and structural phenotypes are used to increase GWAS power and identify novel genes associated with osteoarthritis. Next, , in Chapter 3 also the interaction with the environment is investigated, in partic- ular the use of vitamin K antagonists, to identify novel, and perhaps modifiable, genetic influences associated with osteoarthritis. In Chapter 4 , the results of the largest GWAS to multiple osteoarthritis phenotypes is presented, including functional follow-up to identity possible causal genes. Lastly, in Chapter 5 , the possible influence of the gastro- intestinal microbiome composition on osteoarthritis related knee pain and inflamma- tion is investigated.