Probability and heritability estimates on primary osteoarthritis of the hip leading to total hip arthroplasty: a nationwide population based follow-up study in Danish twins

Søren Glud Skousgaard, Jacob Hjelmborg, Axel Skytthe, Lars Peter Andreas Brandt, Sören Möller, Søren Overgaard, Søren Glud Skousgaard, Jacob Hjelmborg, Axel Skytthe, Lars Peter Andreas Brandt, Sören Möller, Søren Overgaard

Abstract

Introduction: Primary hip osteoarthritis, radiographic as well as symptomatic, is highly associated with increasing age in both genders. However, little is known about the mechanisms behind this, in particular if this increase is caused by genetic factors. This study examined the risk and heritability of primary osteoarthritis of the hip leading to a total hip arthroplasty, and if this heritability increased with increasing age.

Methods: In a nationwide population-based follow-up study 118,788 twins from the Danish Twin Register and 90,007 individuals from the Danish Hip Arthroplasty Register for the period 1995 to 2010 were examined. Our main outcomes were the cumulative incidence, proband-wise concordance and heritability on age, 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 hip arthroplasty at the time of follow-up.

Results: There were 94,063 twins eligible for analyses, comprising 835 cases of 36 concordant and 763 discordant twin pairs. The probability increased particularly from 50 years of age. After sex and age adjustment a significant additive genetic component of 47% (12:79), a shared environmental component of 21% (2:76) and a unique environment component of 32% (21:41) accounted for the variation in population liability to total hip arthroplasty. The sex-adjusted proband-wise concordance and heritability on age indicated an increasing age-associated genetic influence onwards from 60 years of age.

Conclusion: The cumulative incidence in primary hip osteoarthritis leading to total hip arthroplasty increases in particular after the age of 50 years in both genders. Family factors of genes and shared environment are highly significant and account for 68% of the variation in the population liability to total hip arthroplasty; however, the genetic influence increases significantly from 60 years of age onwards.

Figures

Fig. 1
Fig. 1
Flow chart of the participating twins. DHR Dansih Hip Arthroplasty Register, DTR Danish Twin Register, OA Osteoarthritis, THA Total hip arthroplasty
Fig. 2
Fig. 2
Cumulative incidence. Cumulative incidence for THA in males (red line) and females (black line)
Fig. 3
Fig. 3
Proband-wise concordance rate by age in THA, sex-adjusted. DZ Dizygotic, Marginal Background incidence, MZ Monozygotic
Fig. 4
Fig. 4
Heritability of THA by age additive genetic factors only. Sex-adjusted variation in liability to THA from additive genetic factors by age. CI Confidence interval
Fig. 5
Fig. 5
Heritability of THA by age, including the ACE model. Sex-adjusted variation in liability to THA from additive genetic (red line), common (blue line) and unique (green line) environmental factors by age. CI Confidence interval

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