Primary Osteoarthritis of the Hip: A Genetic Disease Caused by European Genetic Variants

Abstract

Primary osteoarthritis of the hip is a separate phenotype that occurs at a rate of 3% to 6% in the populations of the world with European ancestry. In all non-European populations, there is a consistent rarity of primary osteoarthritis that suggests a different etiology for these few patients. Family, sibling, and twin studies prove primary osteoarthritis to be a genetic disease with a 50% heritability caused by European genetic variants. The genetic basis is reinforced by the lower rate of primary osteoarthritis in American minorities consistent with their degree of European gene admixture. Whether the mechanism of degeneration of primary osteoarthritis may be secondary through a morphologic deformity, such as femoroacetabular impingement, remains unknown. The virtual absence of the disease in non-Europeans indicates that the European gene component is necessary for the expression of this separate phenotype of osteoarthritis.

A Heritable Predisposition to Osteoarthritis of the Hip

“…Previous studies have suggested a familial predisposition to hip arthritis and total hip arthroplasty [3][4][5][6][7][8][9][10]. Our data further support the findings of a heritable predisposition to severe osteoarthritis leading to total hip arthroplasty.…”

“…In a recent review of the literature, Hoaglund [6] summarized family, sibling, and twin studies in which primary osteoarthritis was found to be a genetic disease with a 50% heritability caused by European genetic variants. The genetic basis of this finding was reinforced by the lower rate of primary osteoarthritis in American minorities consistent with their degree of European gene admixture.…”

“…Additionally, these methods allow the identification of extended high-risk pedigrees with a statistical excess of disease; these pedigrees provide an informative resource for osteoarthritis predisposition gene identification. Our study used a Utah-based population database of N 1.3 million patients with at least 3 generations of complete ancestral genealogy data (including at least 12 of 14 immediate ancestors) to solidify the earlier suggestions of a genetic predisposition for hip osteoarthritis/THA provided by previous potentially underpowered twin, family and sibling studies and retrospective reviews [3][4][5][6][7][8][9][10]. The inclusion of only those individuals with procedure codes indicating that THA was performed focuses the application of the study to the individuals with presumed symptomatic hip disease and avoids the possibility of misclassification of osteoarthritis by using diagnosis codes only.…”

Lifetime Risk of Primary Total Hip Replacement Surgery for Osteoarthritis From 2003 to 2013: A Multinational Analysis Using National Registry Data

“…Another explanation could be the similar prevalence of hip OA in Australasia and Europe, as demonstrated in the Global Burden of Disease Study (prevalence for females 0.9% in Australasia versus 1.2% in Europe; prevalence for males 0.7% in Australasia versus 0.8–0.9% in Europe) . Hip OA is known to have a strong genetic component and is particularly linked to European genetic variants . This linkage is relevant for the Scandinavian countries as well as for Australia, which has a long history of European migration (68% of Australians report at least 1 type of European ancestry) .…”

Obituary: A Remembrance of Franklin Theodore Hoaglund MD (1930-2014)

“…He specialized in population-based studies, both in the United States and elsewhere. He pursued this interest into his retirement, publishing an already-classic review article [1] spanning epidemiology and genetics at the age of 82 (Fig. 2).…”