Investigation of the Relationship Between Susceptibility Loci for Hip Osteoarthritis and Dual X‐Ray Absorptiometry–Derived Hip Shape in a Population‐Based Cohort of Perimenopausal Women

Denis A Baird, Lavinia Paternoster, Jennifer S Gregory, Benjamin G Faber, Fiona R Saunders, Claudiu V Giuraniuc, Rebecca J Barr, Deborah A Lawlor, Richard M Aspden, Jonathan H. Tobias (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population-based cohort of peri-menopausal women.

METHODS: Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC). The proximal femur and superior acetabulum were outlined, and independent hip shape modes generated. In a sub-regional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA-related SNPs, identified by literature search, and shape modes were analysed in a multivariate canonical correlation analysis.

RESULTS: 3,111 females had genetic and hip shape data (mean 48 years). The KLHDC5-PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P=1x10-5 ). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the sub-regional shape model (P=2x10-3 ). COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the sub-regional shape model (P=5x10-4 ). Regional association plots identified an additional COL11A1 locus in moderate LD with rs4907986, which was more strongly associated with hip shape (rs10047217, P=6x10-6 ). Co-localisation analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC5-PTHLH and COL11A1 loci.

CONCLUSION: Hip OA susceptibility loci were associated with shape in this study suggesting that these loci (and potentially yet to identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)1984-1993
Number of pages10
JournalArthritis & Rheumatology
Volume70
Issue number12
Early online date27 Oct 2018
DOIs
Publication statusPublished - Dec 2018

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Hip Osteoarthritis
Hip
X-Rays
Osteoarthritis
Acetabulum
Alleles
Thigh
Femur
Photon Absorptiometry
Single Nucleotide Polymorphism
Longitudinal Studies
Joints
Parents
Mothers

Keywords

  • Journal Article
  • genetics
  • SSM
  • ALSPAC

Cite this

Investigation of the Relationship Between Susceptibility Loci for Hip Osteoarthritis and Dual X‐Ray Absorptiometry–Derived Hip Shape in a Population‐Based Cohort of Perimenopausal Women. / Baird, Denis A; Paternoster, Lavinia; Gregory, Jennifer S; Faber, Benjamin G; Saunders, Fiona R; Giuraniuc, Claudiu V; Barr, Rebecca J; Lawlor, Deborah A; Aspden, Richard M; Tobias, Jonathan H. (Corresponding Author).

In: Arthritis & Rheumatology, Vol. 70, No. 12, 12.2018, p. 1984-1993.

Research output: Contribution to journalArticle

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abstract = "OBJECTIVE: To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population-based cohort of peri-menopausal women.METHODS: Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC). The proximal femur and superior acetabulum were outlined, and independent hip shape modes generated. In a sub-regional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA-related SNPs, identified by literature search, and shape modes were analysed in a multivariate canonical correlation analysis.RESULTS: 3,111 females had genetic and hip shape data (mean 48 years). The KLHDC5-PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P=1x10-5 ). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the sub-regional shape model (P=2x10-3 ). COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the sub-regional shape model (P=5x10-4 ). Regional association plots identified an additional COL11A1 locus in moderate LD with rs4907986, which was more strongly associated with hip shape (rs10047217, P=6x10-6 ). Co-localisation analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC5-PTHLH and COL11A1 loci.CONCLUSION: Hip OA susceptibility loci were associated with shape in this study suggesting that these loci (and potentially yet to identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development. This article is protected by copyright. All rights reserved.",
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author = "Baird, {Denis A} and Lavinia Paternoster and Gregory, {Jennifer S} and Faber, {Benjamin G} and Saunders, {Fiona R} and Giuraniuc, {Claudiu V} and Barr, {Rebecca J} and Lawlor, {Deborah A} and Aspden, {Richard M} and Tobias, {Jonathan H.}",
note = "This publication is the work of the authors and does not necessarily reflect the views of any funders. Supported by the UK Medical Research Council (grant G1001357 for collection of hip shape), and the Wellcome Trust (grants WT092830M for collection of hip shape and WT088806 for genotyping). Core support for the Avon Longitudinal Study of Parents and Children is provided by the UK Medical Research Council, the Wellcome Trust (102215/2/13/2), and the University of Bristol. Dr. Baird's work was supported by Arthritis Research UK (grant 20244). Mr. Faber's work was supported by an Elizabeth Blackwell Institute Clinical Research Primer Scheme.",
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AU - Baird, Denis A

AU - Paternoster, Lavinia

AU - Gregory, Jennifer S

AU - Faber, Benjamin G

AU - Saunders, Fiona R

AU - Giuraniuc, Claudiu V

AU - Barr, Rebecca J

AU - Lawlor, Deborah A

AU - Aspden, Richard M

AU - Tobias, Jonathan H.

N1 - This publication is the work of the authors and does not necessarily reflect the views of any funders. Supported by the UK Medical Research Council (grant G1001357 for collection of hip shape), and the Wellcome Trust (grants WT092830M for collection of hip shape and WT088806 for genotyping). Core support for the Avon Longitudinal Study of Parents and Children is provided by the UK Medical Research Council, the Wellcome Trust (102215/2/13/2), and the University of Bristol. Dr. Baird's work was supported by Arthritis Research UK (grant 20244). Mr. Faber's work was supported by an Elizabeth Blackwell Institute Clinical Research Primer Scheme.

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N2 - OBJECTIVE: To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population-based cohort of peri-menopausal women.METHODS: Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC). The proximal femur and superior acetabulum were outlined, and independent hip shape modes generated. In a sub-regional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA-related SNPs, identified by literature search, and shape modes were analysed in a multivariate canonical correlation analysis.RESULTS: 3,111 females had genetic and hip shape data (mean 48 years). The KLHDC5-PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P=1x10-5 ). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the sub-regional shape model (P=2x10-3 ). COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the sub-regional shape model (P=5x10-4 ). Regional association plots identified an additional COL11A1 locus in moderate LD with rs4907986, which was more strongly associated with hip shape (rs10047217, P=6x10-6 ). Co-localisation analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC5-PTHLH and COL11A1 loci.CONCLUSION: Hip OA susceptibility loci were associated with shape in this study suggesting that these loci (and potentially yet to identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development. This article is protected by copyright. All rights reserved.

AB - OBJECTIVE: To investigate whether hip shape contributes to osteoarthritis (OA) development, we investigated relationships between known OA susceptibility loci and hip shape in a population-based cohort of peri-menopausal women.METHODS: Hip shape was measured using Statistical Shape Modelling, on hip DXA scans from mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC). The proximal femur and superior acetabulum were outlined, and independent hip shape modes generated. In a sub-regional model, points were restricted to the acetabulum and superior femoral head. Associations between 11 OA-related SNPs, identified by literature search, and shape modes were analysed in a multivariate canonical correlation analysis.RESULTS: 3,111 females had genetic and hip shape data (mean 48 years). The KLHDC5-PTHLH rs10492367 OA risk allele was associated with a wider upper femur in the whole shape model (P=1x10-5 ). The DOT1L rs12982744 OA risk allele was associated with reduced superior joint space in the sub-regional shape model (P=2x10-3 ). COL11A1 rs4907986 OA risk allele was associated with lateral displacement of the femoral head relative to the acetabulum in the sub-regional shape model (P=5x10-4 ). Regional association plots identified an additional COL11A1 locus in moderate LD with rs4907986, which was more strongly associated with hip shape (rs10047217, P=6x10-6 ). Co-localisation analysis indicated sharing of genetic signals for hip shape and hip OA for the KLHDC5-PTHLH and COL11A1 loci.CONCLUSION: Hip OA susceptibility loci were associated with shape in this study suggesting that these loci (and potentially yet to identified hip OA loci) could contribute to hip OA in later life via perturbing biologic pathways that mediate morphology development. This article is protected by copyright. All rights reserved.

KW - Journal Article

KW - genetics

KW - SSM

KW - ALSPAC

U2 - 10.1002/art.40584

DO - 10.1002/art.40584

M3 - Article

VL - 70

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JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

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