Cindy Boer

136 | Chapter 3.2 We therefore examined the relation of VKA use to progression and incidence of hip and knee OA in two subcohorts of the large prospective population-based cohort of the Rotterdam Study. We additionally examined how the impact of VKA use varies by presence of the MGP risk allele that influences MGP expression and SNVs affecting VKORC1 gene expression, which impact VKA dosage. Methods Study population and clinical data The Rotterdam study (RS) is a large prospective population-based cohort study ongoing since 1990 to study determinants of chronic disabling diseases in the elderly[14]. It consists of separate subcohorts (RS-I, RS-II, RS-III). All RS cohort participants live in the Ommoord district of the city of Rotterdam, the Netherlands. Residents of 55 years and older were first recruited in 1990. In 2000, a second cohort, RS-II, was started with indi- viduals who had become 55 years of age or moved into the study district since the start of the study. Follow-up data were collected as follow-up visits every ~5-6 years. Details of the design and rationale of the Rotterdam Study has been published elsewhere[14]. Participant measurements at baseline and follow-up were obtained during visits to the research center for physical examinations, computerized pharmacy records, and from home interviews. Our study included participants of RS-I and RS-II for whom radio- graphs of knee and hip joints at baseline and follow-up visit were present, obtained and scored ( Supplementary Figure S1 ). Additional information included: sex, age at baseline visit, body mass index (BMI, kg-1m2), physical activity (metabolic equivalent of task/hours per week), smoking (never, former and current smoker), locomotor dis- ability, education level (UNESCO education classification), Diabetes mellitus, hyperten- sion, femoral neck bone mineral density (FN-BMD), HDL/total cholesterol ratio and the Stanford Health Assessment Questionnaire ( see Supplementary Text for details ). The Rotterdam Study has been approved by the institutional review board (Med- ical Ethics Committee) of the Erasmus Medical Center and by the review board of The Netherlands Ministry of Health, Welfare and Sports. The approval has been renewed every 5 years (MEC 02.1015). All participants provided written informed consent for participation in the Rotterdam Study. Incidence and Progression of OA Our study included participants of RS-I and RS-II for whom radiographs of knee and hip joints at baseline and follow-up visit were obtained and scored by trained medical