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BMD-related genetic risk scores predict site-specific fractures as well as trabecular and cortical bone microstructure
Nethander, Maria Pettersson-Kymmer, Ulrika Vandenput, Liesbeth Lorentzon, Mattias Karlsson, Magnus Mellström, Dan Ohlsson, Claes
Nethander, Maria
Pettersson-Kymmer, Ulrika
Vandenput, Liesbeth
Lorentzon, Mattias
Karlsson, Magnus
Mellström, Dan
Ohlsson, Claes
Abstract
Context
It is important to identify patients at highest risk of fractures.
Objective
To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately.
Design, Setting, and Participants
Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort.
Results
We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters.
Conclusions
The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
Keywords
bone mineral density, genetic risk scores, fractures, bone microstructure, trabecular, cortical
Date
2020
Type
Journal article
Journal
The Journal of Clinical Endocrinology and Metabolism
Book
Volume
105
Issue
4
Page Range
e1344-e1357
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open