Obesity variants in the GIPR gene do not associate with risk of fracture or bone mineral density

Unnur Styrkarsdottir, Vinicius Tragante, Lilja Stefansdottir, Gudmar Thorleifsson, Asmundur Oddsson, Erik Sørensen, Christian Erikstrup, Peter Schwarz, Henrik Løvendahl Jørgensen, Jes Bruun Lauritzen, Søren Brunak, Kirk U Knowlton, Lincoln D Nadauld, Henrik Ullum, Ole Birger Vesterager Pedersen, Sisse Rye Ostrowski, Hilma Holm, Daniel F Gudbjartsson, Patrick Sulem, Kari Stefansson*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstract

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.

OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
DOI
StatusUdgivet, E-publikation før trykning - 20 dec. 2023

Bibliografisk note

© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

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