Obesity variants in the GIPR gene do not associate with risk of fracture or bone mineral density
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Obesity variants in the GIPR gene do not associate with risk of fracture or bone mineral density. / Styrkarsdottir, Unnur; Tragante, Vinicius; Stefansdottir, Lilja; Thorleifsson, Gudmar; Oddsson, Asmundur; Sørensen, Erik; Erikstrup, Christian; Schwarz, Peter; Jørgensen, Henrik Løvendahl; Lauritzen, Jes Bruun; Brunak, Søren; Knowlton, Kirk U; Nadauld, Lincoln D; Ullum, Henrik; Pedersen, Ole Birger Vesterager; Ostrowski, Sisse Rye; Holm, Hilma; Gudbjartsson, Daniel F; Sulem, Patrick; Stefansson, Kari.
In: Journal of Clinical Endocrinology and Metabolism, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Obesity variants in the GIPR gene do not associate with risk of fracture or bone mineral density
AU - Styrkarsdottir, Unnur
AU - Tragante, Vinicius
AU - Stefansdottir, Lilja
AU - Thorleifsson, Gudmar
AU - Oddsson, Asmundur
AU - Sørensen, Erik
AU - Erikstrup, Christian
AU - Schwarz, Peter
AU - Jørgensen, Henrik Løvendahl
AU - Lauritzen, Jes Bruun
AU - Brunak, Søren
AU - Knowlton, Kirk U
AU - Nadauld, Lincoln D
AU - Ullum, Henrik
AU - Pedersen, Ole Birger Vesterager
AU - Ostrowski, Sisse Rye
AU - Holm, Hilma
AU - Gudbjartsson, Daniel F
AU - Sulem, Patrick
AU - Stefansson, Kari
N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024
Y1 - 2024
N2 - OBJECTIVE: The objective of this study was to investigate the risk of fracture and bone mineral density (BMD) of sequence variants in GIPR that reduce the activity of the GIPR receptor and have been associated with reduced body mass index (BMI).METHODS: We analysed the association of three missense variants in GIPR, a common variant, rs1800437 (p.Glu354Gln), and two rare variants, rs139215588 (p.Arg190Gln) and rs143430880 (p.Glu288Gly), as well as a burden of predicted loss of function (LoF) variants with risk of fracture and with BMD in a large meta-analysis of up to 1.2 million participants. We analysed associations with fractures at different skeletal sites in the general population; any fractures, hip fractures, vertebral fractures and forearm fractures, and specifically non-vertebral and osteoporotic fractures in postmenopausal women. We also evaluated associations with BMD at the lumbar spine, femoral neck, and total body measured with dual-energy X-ray absorptiometry (DXA), and with BMD estimated from heel ultrasound (eBMD).RESULTS: None of the three missense variants in GIPR associated significantly with increased risk of fractures or with lower BMD. Burden of LoF variants in GIPR were not associated with fractures or with BMD measured with clinically validated DXA, but associated with eBMD.CONCLUSION: Missense variants in GIPR, or burden of LoF variants in the gene, do not associate with risk of fractures or with lower BMD.
AB - OBJECTIVE: The objective of this study was to investigate the risk of fracture and bone mineral density (BMD) of sequence variants in GIPR that reduce the activity of the GIPR receptor and have been associated with reduced body mass index (BMI).METHODS: We analysed the association of three missense variants in GIPR, a common variant, rs1800437 (p.Glu354Gln), and two rare variants, rs139215588 (p.Arg190Gln) and rs143430880 (p.Glu288Gly), as well as a burden of predicted loss of function (LoF) variants with risk of fracture and with BMD in a large meta-analysis of up to 1.2 million participants. We analysed associations with fractures at different skeletal sites in the general population; any fractures, hip fractures, vertebral fractures and forearm fractures, and specifically non-vertebral and osteoporotic fractures in postmenopausal women. We also evaluated associations with BMD at the lumbar spine, femoral neck, and total body measured with dual-energy X-ray absorptiometry (DXA), and with BMD estimated from heel ultrasound (eBMD).RESULTS: None of the three missense variants in GIPR associated significantly with increased risk of fractures or with lower BMD. Burden of LoF variants in GIPR were not associated with fractures or with BMD measured with clinically validated DXA, but associated with eBMD.CONCLUSION: Missense variants in GIPR, or burden of LoF variants in the gene, do not associate with risk of fractures or with lower BMD.
U2 - 10.1210/clinem/dgad734
DO - 10.1210/clinem/dgad734
M3 - Journal article
C2 - 38118020
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
ER -
ID: 378866838