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Sex differences in risk and heritability estimates on primary knee osteoarthritis leading to total knee arthroplasty: a nationwide population based follow up study in Danish twins.
Arthritis Res Ther. 2016 Feb 11; 18:46.AR

Abstract

BACKGROUND

Symptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability.

METHODS

All twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up.

RESULTS

92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50 years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18 % (0; 62), a shared environmental component of 61 % (25; 97) and an individual environmental component of 21 % (6; 36) accounted for the variation in liability to primary total knee arthroplasty.

CONCLUSION

The risk of primary total knee arthroplasty increases significantly after the age of 50 years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82 % of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18 % of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease.

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Authors+Show Affiliations

Skousgaard SG
Department of Occupational and Environmental Medicine, Odense University Hospital, 5000, Odense C, Denmark. soeren.skousgaard@rsyd.dk. Department of Orthopaedic Surgery and Traumatology & Orthopedic Research Unit, Institute of Clinical Research, University of Southern Denmark, 5000, Odense C, Denmark. soeren.skousgaard@rsyd.dk. Clinical Institute, University of Southern Denmark, 5000, Odense C, Denmark. soeren.skousgaard@rsyd.dk.
Skytthe A
Department of Epidemiology, Biostatistics and Biodemography, The Danish Twin Registry, University of Southern Denmark, 5000, Odense C, Denmark. ASkytthe@health.sdu.dk.
Möller S
Department of Epidemiology, Biostatistics and Biodemography, The Danish Twin Registry, University of Southern Denmark, 5000, Odense C, Denmark. moeller@health.sdu.dk.
Overgaard S
Department of Orthopaedic Surgery and Traumatology & Orthopedic Research Unit, Institute of Clinical Research, University of Southern Denmark, 5000, Odense C, Denmark. soeren.overgaard@rsyd.dk. Clinical Institute, University of Southern Denmark, 5000, Odense C, Denmark. soeren.overgaard@rsyd.dk.
Brandt LP
Department of Occupational and Environmental Medicine, Odense University Hospital, 5000, Odense C, Denmark. lars.brandt@rsyd.dk. Clinical Institute, University of Southern Denmark, 5000, Odense C, Denmark. lars.brandt@rsyd.dk.

MeSH

AdolescentAdultAgedAged, 80 and overArthroplasty, Replacement, KneeDenmarkDiseases in TwinsFemaleFollow-Up StudiesHumansMaleMiddle AgedOsteoarthritis, KneePopulation SurveillanceQuantitative Trait, HeritableRegistriesRisk FactorsSex CharacteristicsTwins, DizygoticTwins, MonozygoticYoung Adult

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

26864139

Clinical Trial Links

The Marigot Osteoarthritis Nutritional Intervention (MOANi) Trial

Citation

Skousgaard, Søren Glud, et al. "Sex Differences in Risk and Heritability Estimates On Primary Knee Osteoarthritis Leading to Total Knee Arthroplasty: a Nationwide Population Based Follow Up Study in Danish Twins." Arthritis Research & Therapy, vol. 18, 2016, p. 46.
Skousgaard SG, Skytthe A, Möller S, et al. Sex differences in risk and heritability estimates on primary knee osteoarthritis leading to total knee arthroplasty: a nationwide population based follow up study in Danish twins. Arthritis Res Ther. 2016;18:46.
Skousgaard, S. G., Skytthe, A., Möller, S., Overgaard, S., & Brandt, L. P. (2016). Sex differences in risk and heritability estimates on primary knee osteoarthritis leading to total knee arthroplasty: a nationwide population based follow up study in Danish twins. Arthritis Research & Therapy, 18, 46. https://doi.org/10.1186/s13075-016-0939-8
Skousgaard SG, et al. Sex Differences in Risk and Heritability Estimates On Primary Knee Osteoarthritis Leading to Total Knee Arthroplasty: a Nationwide Population Based Follow Up Study in Danish Twins. Arthritis Res Ther. 2016 Feb 11;18:46. PubMed PMID: 26864139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex differences in risk and heritability estimates on primary knee osteoarthritis leading to total knee arthroplasty: a nationwide population based follow up study in Danish twins. AU - Skousgaard,Søren Glud, AU - Skytthe,Axel, AU - Möller,Sören, AU - Overgaard,Søren, AU - Brandt,Lars Peter Andreas, Y1 - 2016/02/11/ PY - 2015/11/19/received PY - 2016/01/19/accepted PY - 2016/2/12/entrez PY - 2016/2/13/pubmed PY - 2016/10/8/medline SP - 46 EP - 46 JF - Arthritis research & therapy JO - Arthritis Res Ther VL - 18 N2 - BACKGROUND: Symptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability. METHODS: All twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up. RESULTS: 92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50 years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18 % (0; 62), a shared environmental component of 61 % (25; 97) and an individual environmental component of 21 % (6; 36) accounted for the variation in liability to primary total knee arthroplasty. CONCLUSION: The risk of primary total knee arthroplasty increases significantly after the age of 50 years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82 % of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18 % of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/26864139/Sex_differences_in_risk_and_heritability_estimates_on_primary_knee_osteoarthritis_leading_to_total_knee_arthroplasty:_a_nationwide_population_based_follow_up_study_in_Danish_twins_ DB - PRIME DP - Unbound Medicine ER -