Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

Katherine S Elliott; Kay Chapman; Aaron Day-Williams; Kalliope Panoutsopoulou; Lorraine Southam; Cecilia M Lindgren; Nigel Arden; Nadim Aslam; Fraser Birrell; Ian Carluke; Andrew Carr; Panos Deloukas; Michael Doherty; John Loughlin; Andrew McCaskie; William E R Ollier; Ashok Rai; Stuart Ralston; Mike R Reed; Timothy D Spector; Ana M Valdes; Gillian A Wallis; Mark Wilkinson; Eleftheria Zeggini; GIANT consortium

doi:10.1136/annrheumdis-2012-202081

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

Katherine S Elliott, Kay Chapman, Aaron Day-Williams, Kalliope Panoutsopoulou, Lorraine Southam, Cecilia M Lindgren, Nigel Arden, Nadim Aslam, Fraser Birrell, Ian Carluke, Andrew Carr, Panos Deloukas, Michael Doherty, John Loughlin, Andrew McCaskie, William E R Ollier, Ashok Rai, Stuart Ralston, Mike R Reed, Timothy D SpectorAna M Valdes, Gillian A Wallis, Mark Wilkinson, Eleftheria Zeggini, GIANT consortium

University of Oxford

Research output: Contribution to journal › Article › peer-review

41 Citations (Scopus)

Abstract

OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.

METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.

RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.

CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

Original language	English
Pages (from-to)	935-41
Number of pages	7
Journal	Annals of the rheumatic diseases
Volume	72
Issue number	6
DOIs	https://doi.org/10.1136/annrheumdis-2012-202081
Publication status	Published - Jun 2013

Keywords

Adult
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Body Height
Body Mass Index
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Obesity
Osteoarthritis
Polymorphism, Single Nucleotide
Proteins
Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1136/annrheumdis-2012-202081Licence: CC BY-NC

Cite this

Elliott, K. S., Chapman, K., Day-Williams, A., Panoutsopoulou, K., Southam, L., Lindgren, C. M., Arden, N., Aslam, N., Birrell, F., Carluke, I., Carr, A., Deloukas, P., Doherty, M., Loughlin, J., McCaskie, A., Ollier, W. E. R., Rai, A., Ralston, S., Reed, M. R., ... GIANT consortium (2013). Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data. Annals of the rheumatic diseases, 72(6), 935-41. https://doi.org/10.1136/annrheumdis-2012-202081

@article{e8b81941f6d342289035d994f1ea39e1,

title = "Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data",

abstract = "OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.",

keywords = "Adult, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Height, Body Mass Index, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity, Osteoarthritis, Polymorphism, Single Nucleotide, Proteins, Journal Article, Research Support, Non-U.S. Gov't",

author = "Elliott, {Katherine S} and Kay Chapman and Aaron Day-Williams and Kalliope Panoutsopoulou and Lorraine Southam and Lindgren, {Cecilia M} and Nigel Arden and Nadim Aslam and Fraser Birrell and Ian Carluke and Andrew Carr and Panos Deloukas and Michael Doherty and John Loughlin and Andrew McCaskie and Ollier, {William E R} and Ashok Rai and Stuart Ralston and Reed, {Mike R} and Spector, {Timothy D} and Valdes, {Ana M} and Wallis, {Gillian A} and Mark Wilkinson and Eleftheria Zeggini and {GIANT consortium}",

year = "2013",

month = jun,

doi = "10.1136/annrheumdis-2012-202081",

language = "English",

volume = "72",

pages = "935--41",

journal = "Annals of the rheumatic diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "6",

}

Elliott, KS, Chapman, K, Day-Williams, A, Panoutsopoulou, K, Southam, L, Lindgren, CM, Arden, N, Aslam, N, Birrell, F, Carluke, I, Carr, A, Deloukas, P, Doherty, M, Loughlin, J, McCaskie, A, Ollier, WER, Rai, A, Ralston, S, Reed, MR, Spector, TD , Valdes, AM, Wallis, GA, Wilkinson, M, Zeggini, E & GIANT consortium 2013, 'Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data', Annals of the rheumatic diseases, vol. 72, no. 6, pp. 935-41. https://doi.org/10.1136/annrheumdis-2012-202081

TY - JOUR

T1 - Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

AU - Elliott, Katherine S

AU - Chapman, Kay

AU - Day-Williams, Aaron

AU - Panoutsopoulou, Kalliope

AU - Southam, Lorraine

AU - Lindgren, Cecilia M

AU - Arden, Nigel

AU - Aslam, Nadim

AU - Birrell, Fraser

AU - Carluke, Ian

AU - Carr, Andrew

AU - Deloukas, Panos

AU - Doherty, Michael

AU - Loughlin, John

AU - McCaskie, Andrew

AU - Ollier, William E R

AU - Rai, Ashok

AU - Ralston, Stuart

AU - Reed, Mike R

AU - Spector, Timothy D

AU - Valdes, Ana M

AU - Wallis, Gillian A

AU - Wilkinson, Mark

AU - Zeggini, Eleftheria

AU - GIANT consortium

PY - 2013/6

Y1 - 2013/6

N2 - OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

AB - OBJECTIVES: Obesity as measured by body mass index (BMI) is one of the major risk factors for osteoarthritis. In addition, genetic overlap has been reported between osteoarthritis and normal adult height variation. We investigated whether this relationship is due to a shared genetic aetiology on a genome-wide scale.METHODS: We compared genetic association summary statistics (effect size, p value) for BMI and height from the GIANT consortium genome-wide association study (GWAS) with genetic association summary statistics from the arcOGEN consortium osteoarthritis GWAS. Significance was evaluated by permutation. Replication of osteoarthritis association of the highlighted signals was investigated in an independent dataset. Phenotypic information of height and BMI was accounted for in a separate analysis using osteoarthritis-free controls.RESULTS: We found significant overlap between osteoarthritis and height (p=3.3×10(-5) for signals with p≤0.05) when the GIANT and arcOGEN GWAS were compared. For signals with p≤0.001 we found 17 shared signals between osteoarthritis and height and four between osteoarthritis and BMI. However, only one of the height or BMI signals that had shown evidence of association with osteoarthritis in the arcOGEN GWAS was also associated with osteoarthritis in the independent dataset: rs12149832, within the FTO gene (combined p=2.3×10(-5)). As expected, this signal was attenuated when we adjusted for BMI.CONCLUSIONS: We found a significant excess of shared signals between both osteoarthritis and height and osteoarthritis and BMI, suggestive of a common genetic aetiology. However, only one signal showed association with osteoarthritis when followed up in a new dataset.

KW - Adult

KW - Alpha-Ketoglutarate-Dependent Dioxygenase FTO

KW - Body Height

KW - Body Mass Index

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Obesity

KW - Osteoarthritis

KW - Polymorphism, Single Nucleotide

KW - Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1136/annrheumdis-2012-202081

DO - 10.1136/annrheumdis-2012-202081

M3 - Article

C2 - 22956599

SN - 0003-4967

VL - 72

SP - 935

EP - 941

JO - Annals of the rheumatic diseases

JF - Annals of the rheumatic diseases

IS - 6

ER -

Evaluation of the genetic overlap between osteoarthritis with body mass index and height using genome-wide association scan data

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this