Investigation of the genetic susceptibility to osteoporosis in the Irish population

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dc.contributor.advisor Molloy, Michael en
dc.contributor.advisor Drummond, Frances en Hegarty, Kevin G. 2014-03-25T12:51:09Z 2013 2013
dc.identifier.citation Hegarty, K. G. 2013. Investigation of the genetic susceptibility to osteoporosis in the Irish population. PhD Thesis, University College Cork. en
dc.description.abstract Osteoporosis is a complex skeletal disorder characterized by compromised bone strength. Variation in bone mineral density (BMD) is a contributing factor. The aim of this research as to select informative single nucleotide polymorphisms (SNPs) in potential candidate genes from loci suggestively linked to BMD variation for fine mapping. The gene regulated by oestrogen in breast cancer 1 (GREB1), located at 2p25.1, was selected. GREB1 transcription is initiated early in the oestrogen receptor alpha regulated pathway. There was significant association between GREB1_03 and BMD variation at the lumbar spine and femoral neck (FN) in the discovery cohort. Significant association was observed between GREB1_04 and FN BMD in the replication cohort. The development and differentiation enhancing factor 2, the integrin cytoplasmic domain associated protein 1 and A-disintegrin and metalloprotease 17 were selected due to their respective roles in cell mobility and adhesion. There was no linkage or association observed between the Chr2 cluster SNPs and BMD. Two factors in bone remodelling are the attraction of bone cell precursors and endocrine regulation of the process, primarily through the action of parathyroid hormone (PTH). The C-C chemokine receptor type 3 (CCR3) encodes a CC chemokine receptor expressed in osteoclast precursors. The PTH receptor type 1 (PTHR1) encodes a G-protein coupled receptor for PTH. Association was observed between CCR3 haplotypes and BMD variation at the FN. There was no linkage or association observed between PTHR1 SNPs and BMD variation. Population genetic studies with complex phenotypes endeavour to elucidate the traits genetic architecture. This study presents evidence of association between GREB1 and BMD variation and as such, introduces GREB1 as a novel gene target for osteoporosis genetics studies. It affirms that common genomic variants in PTHR1 are not associated with BMD variation in Caucasians and supports the evidence that CCR3 may be contributing to BMD variation en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2013, Kevin G. Hegarty en
dc.rights.uri en
dc.subject Genetics en
dc.subject.lcsh Osteoporosis en
dc.title Investigation of the genetic susceptibility to osteoporosis in the Irish population en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Indefinite en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Irish Centre for Arthritis Research and Education en
dc.description.status Not peer reviewed en Medicine en
dc.check.type No Embargo Required
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.embargoformat Hard bound copy in Library only en
dc.internal.conferring Spring Conferring 2014 en

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© 2013, Kevin G. Hegarty Except where otherwise noted, this item's license is described as © 2013, Kevin G. Hegarty
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