Cindy Boer

Hand Osteoarthritis Phenotypes | 107 2.2 available chondrogenic source material, indicating a more general role for the WNT9A locus in chondrocyte functional pathways. Given the complex nature of OA susceptibility and the fact that pathophysiologic causes are not uniform across skeletal sites, alterations in WNT9A expression may be seen in other joints, but may have a more marked detrimental effect on the thumb joints. In summary, by examining the distribution of radiographic OA features in the hand joints, we identified three distinct hand OA phenotypes that provided the basis for identification of a novel locus for thumb OA despite our modest sample size. We iden-tified WNT9A as a plausible causal gene for thumb OA, providing new insights into the genetic architecture of hand OA and a new candidate for OA therapeutic development. Supplementary matarial All supplementary materials: Methods, Figures and Tables, Can be viewed and down-loaded online at this location: https://drive.google.com/ drive/folders/1iqiLVJm1MbeNhefsbLNzQhLNmvHhj5OB?usp=sharing Data Availability Statement All relevant data supporting the key findings of this study are available within the ar- ticle and its supplementary information files. Other data are available from the corre- sponding author upon reasonable request. Due to ethical and legal restrictions, indi-vidual-level data of the Rotterdam Study (RS) cannot be made publicly available. Data are available upon request to the data manager of the Rotterdam Study Frank van Rooij (f.vanrooij@erasmusmc.nl ) and subject to local rules and regulations. This includes submitting a proposal to the management team of RS, where upon approval, analysis needs to be done on a local server with protected access, complying with GDPR regula-tions. Acknowledgments The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and man-agement of GWAS genotype data for the Rotterdam Study (RS I, RS II, RS III) was exe-cuted by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Linda Broer PhD, for the creation of the imputed data.