Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation

Maria K Sobczyk-Barad; Ben G Faber; Lorraine Southam; Monika R Frysz; April E Hartley; Eleftheria Zeggini; Haotian Tang; Tom R Gaunt; et al

doi:10.1016/j.joca.2023.12.003

Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation

Maria K Sobczyk-Barad^*, Ben G Faber, Lorraine Southam, Monika R Frysz, April E Hartley, Eleftheria Zeggini, Haotian Tang, Tom R Gaunt, et al

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

2 Citations (Scopus)

Abstract

Objective
Spinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques.

Design
We applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified.

Results
Our analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10−21), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10−3) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10−6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10−7), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10−7), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10−11). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (ORallOA = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR.

Conclusions
Genetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.

Original language	English
Number of pages	11
Journal	Osteoarthritis and Cartilage
DOIs	https://doi.org/10.1016/j.joca.2023.12.003
Publication status	Published - 30 Dec 2023

Bibliographical note

Funding Information:
This work was funded by the UK Medical Research Council (MRC) as part of the MRC Integrative Epidemiology Unit ( MC_UU_00032/03 ). This study was supported by the National Institute for Health and Care Bristol Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. BGF is funded by an NIHR Academic Clinical Lectureship. MF is funded by a Wellcome Trust collaborative award (reference number 209233 ). The funders had no role in the study design, collection, analysis or interpretation of data, writing of the manuscript or in the decision to submit the manuscript for publication.

Funding Information:
TRG receives funding from Biogen for unrelated research.

Publisher Copyright:
© 2024 The Authors

Keywords

Spinal stenosis
Lumbar stenosis
Osteoarthritis
Body mass index
Bone mineral density
Mendelian randomisation

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@article{929d3555bd6546c684d6b1d5637d6a8c,

title = "Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation",

abstract = "ObjectiveSpinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques.DesignWe applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified.ResultsOur analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10−21), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10−3) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10−6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10−7), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10−7), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10−11). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (ORallOA = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR.ConclusionsGenetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.",

keywords = "Spinal stenosis, Lumbar stenosis, Osteoarthritis, Body mass index, Bone mineral density, Mendelian randomisation",

author = "Sobczyk-Barad, {Maria K} and Faber, {Ben G} and Lorraine Southam and Frysz, {Monika R} and Hartley, {April E} and Eleftheria Zeggini and Haotian Tang and Gaunt, {Tom R} and et al",

note = "Funding Information: This work was funded by the UK Medical Research Council (MRC) as part of the MRC Integrative Epidemiology Unit ( MC_UU_00032/03 ). This study was supported by the National Institute for Health and Care Bristol Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. BGF is funded by an NIHR Academic Clinical Lectureship. MF is funded by a Wellcome Trust collaborative award (reference number 209233 ). The funders had no role in the study design, collection, analysis or interpretation of data, writing of the manuscript or in the decision to submit the manuscript for publication. Funding Information: TRG receives funding from Biogen for unrelated research. Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2023",

month = dec,

day = "30",

doi = "10.1016/j.joca.2023.12.003",

language = "English",

journal = "Osteoarthritis and Cartilage",

issn = "1063-4584",

publisher = "W.B. Saunders",

}

TY - JOUR

T1 - Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis

T2 - A Mendelian randomisation investigation

AU - Sobczyk-Barad, Maria K

AU - Faber, Ben G

AU - Southam, Lorraine

AU - Frysz, Monika R

AU - Hartley, April E

AU - Zeggini, Eleftheria

AU - Tang, Haotian

AU - Gaunt, Tom R

AU - al, et

N1 - Funding Information: This work was funded by the UK Medical Research Council (MRC) as part of the MRC Integrative Epidemiology Unit ( MC_UU_00032/03 ). This study was supported by the National Institute for Health and Care Bristol Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. BGF is funded by an NIHR Academic Clinical Lectureship. MF is funded by a Wellcome Trust collaborative award (reference number 209233 ). The funders had no role in the study design, collection, analysis or interpretation of data, writing of the manuscript or in the decision to submit the manuscript for publication. Funding Information: TRG receives funding from Biogen for unrelated research. Publisher Copyright: © 2024 The Authors

PY - 2023/12/30

Y1 - 2023/12/30

N2 - ObjectiveSpinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques.DesignWe applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified.ResultsOur analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10−21), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10−3) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10−6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10−7), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10−7), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10−11). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (ORallOA = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR.ConclusionsGenetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.

AB - ObjectiveSpinal stenosis is a common condition among older individuals, with significant morbidity attached. Little is known about its risk factors but degenerative conditions, such as osteoarthritis (OA) have been identified for their mechanistic role. This study aims to explore causal relationships between anthropometric risk factors, OA, and spinal stenosis using Mendelian randomisation (MR) techniques.DesignWe applied two-sample MR to investigate the causal relationships between genetic liability for select risk factors and spinal stenosis. Next, we examined the genetic relationship between OA and spinal stenosis with linkage disequilibrium score regression and Causal Analysis Using Summary Effect estimates MR method. Finally, we used multivariable MR (MVMR) to explore whether OA and body mass index (BMI) mediate the causal pathways identified.ResultsOur analysis revealed strong evidence for the effect of higher BMI (odds ratio [OR] = 1.54, 95%CI: 1.41-1.69, p-value = 2.7 × 10−21), waist (OR = 1.43, 95%CI: 1.15-1.79, p-value = 1.5 × 10−3) and hip (OR = 1.50, 95%CI: 1.27-1.78, p-value = 3.3 × 10−6) circumference on spinal stenosis. Strong evidence of causality was also observed for higher bone mineral density (BMD): total body (OR = 1.21, 95%CI: 1.12-1.29, p-value = 1.6 × 10−7), femoral neck (OR = 1.35, 95%CI: 1.09-1.37, p-value = 7.5×10−7), and lumbar spine (OR = 1.38, 95%CI: 1.25-1.52, p-value = 4.4 × 10−11). We detected high genetic correlations between spinal stenosis and OA (rg range: 0.47-0.66), with Causal Analysis Using Summary Effect estimates results supporting a causal effect of OA on spinal stenosis (ORallOA = 1.6, 95%CI: 1.41-1.79). Direct effects of BMI, BMD on spinal stenosis remained after adjusting for OA in the MVMR.ConclusionsGenetic susceptibility to anthropometric risk factors, particularly higher BMI and BMD can increase the risk of spinal stenosis, independent of OA status. These results may inform preventative strategies and treatments.

KW - Spinal stenosis

KW - Lumbar stenosis

KW - Osteoarthritis

KW - Body mass index

KW - Bone mineral density

KW - Mendelian randomisation

U2 - 10.1016/j.joca.2023.12.003

DO - 10.1016/j.joca.2023.12.003

M3 - Article (Academic Journal)

C2 - 38160745

SN - 1063-4584

JO - Osteoarthritis and Cartilage

JF - Osteoarthritis and Cartilage

ER -

Causal relationships between anthropometric traits, bone mineral density, osteoarthritis and spinal stenosis: A Mendelian randomisation investigation

Abstract

Bibliographical note

Keywords

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