In this thesis, we found that a) low bone mineral density was related to increased mortality from chronic obstructive pulmonary disease and b) increased serum phosphate, even at normal levels, was related to fracture risk, low BMD at the lumbar spine and coronary artery calcification. For the latter association, we found evidence of causality, due to the implementation of Mendelian Randomization technique. All our results were more consistent or even unique in men. The genetic analyses on phosphate levels identified 264 loci in the human genome and highlighted the importance of the Major Histocompatibility Complex (6p21.3) also on phosphate levels, as the top hit mapped to the flanking region of the MHC. Interestingly, the same finding has been described in White British and East Asian Japanese populations. Our next step will be the replication in BioBank Japan followed by trans-ethnic meta-analysis and Bayesian fine-mapping.

Additional Metadata
Keywords low bone mineral density, phosphate, chronic obstructive pulmonary disease, coronary artery calcification, genome-wide association study, Bayesian fine-mapping
Promotor M.C. Zillikens (Carola) , A.G. Uitterlinden (André)
Publisher Erasmus University Rotterdam
ISBN 978-9968-48-518-9
Persistent URL hdl.handle.net/1765/127238
Note For copyright reasons there is a partial embargo for this dissertation
Citation
Campos-Obando, N. (2020, May 28). Bone and Phosphate in Relation to Health, Survival and Genetic Factors. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/127238