Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank.

OBJECTIVE: Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after a knee injury and its genetic associations in UK Biobank (UKB). DESIGN: Clinically significant structural knee injuries in those ≤50 years were identified from electronic health records and self-reported data in 502,409 UKB participants. Time-to-first knee osteoarthritis (OA) code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months to 20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought. RESULTS: Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD 10.4]). Over a median of 30.2 (IQR 19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81 (1.70,1.93), P = 8.9 × 10-74. Female sex and increasing age at injury were associated with knee OA following injury (HR 1.15 [1.02,1.30];1.07 [1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR 3.26 [2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43 [0.02,8.41]). CONCLUSIONS: Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA.

Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Submaximal fatigue and recovery in boys and men.

We examined the effects of a sustained submaximal isometric contraction on fatigue and recovery rates in untrained prepubescent boys and men. Fifteen prepubescent boys and 15 men executed an isometric plantar flexion at 20% of their maximal voluntary contraction for 10 min. During the fatigue protocol, surface electromyogram of the soleus, medial gastrocnemius, and tibialis anterior muscles were obtained. Following the fatigue protocol, maximal voluntary contraction data were also obtained every 3 min throughout a 15-min recovery period. During the fatigue protocol, agonist and antagonist surface electromyogram increased gradually to a similar extent in both groups. Following fatigue, torque and surface electromyogram during a maximal voluntary contraction decreased compared to pre-fatigue values and recovered in a similar manner in both groups. However, boys showed faster recovery in torque and surface electromyogram during the third minute of recovery period. It is concluded that a low-intensity sustained isometric fatigue protocol induces similar fatigue levels in boys and men. However, there is evidence that boys can recover faster than men.

Agonist and antagonist muscle activation during maximal and submaximal isokinetic fatigue tests of the knee extensors.

The purpose of this study was to examine the differences in electromyographic activity of agonist and antagonist knee musculature between a maximal and a submaximal isokinetic fatigue protocol. Fourteen healthy males (age: 24.3+/-2.5 years) performed 25 maximal (MIFP) and 60 submaximal (SIFP) isokinetic concentric efforts of the knee extensors at 60 degrees s(-1), across a 90 degrees range of motion. The two protocols were performed a week apart. The EMG activity of vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) were recorded using surface electrodes. The peak torque (PT) and average EMG (aEMG) were expressed as percentages of pre-fatigue maximal value. One-way analysis of variance indicated a significant (p<0.05) decline of PT during the maximal (45.7%) and submaximal (46.8%) protocols. During the maximal test, the VM and VL aEMG initially increased and then decreased. In contrast, VM and VL aEMG continuously increased during submaximal testing (p<0.05). The antagonist (BF) aEMG remained constant during maximal test but it increased significantly and then declined during the submaximal testing. The above results indicate that agonist and antagonist activity depends on the intensity of the selected isokinetic fatigue test.

Fatigue differences between adults and prepubertal males.

The purpose of the present study was to investigate the differences in neuromuscular activation of agonist and antagonist muscles between men and prepubertal boys during a maximal isokinetic fatigue test. Ten prepubertal boys (mean +/- SD age: 10.5 +/- 0.6 years) and fourteen adults (age: 24.3 +/- 2.5 years) executed 25 consecutive maximal isokinetic knee extensions at 60 deg . s (-1). Peak torque and the electromyogram (EMG) of the vastus lateralis, vastus medialis and biceps femoris muscles were recorded. During the fatigue protocol, the prepubertal boys were able to produce higher torque than the adults, when expressed as percent of their maximal value, indicating that adults were more fatigable. The agonist activity, especially for the vastus lateralis muscle, increased in both groups during the first 10 knee extensions, and then decreased more in adults. The antagonist activity of biceps femoris muscle in adults remained constant throughout the fatigue task, whereas the children showed, on average, an increased biceps femoris antagonistic activation, especially during the first 10 and last 5 knee extensions. These results suggest that adults are more fatigable than children during a maximal isokinetic fatigue protocol, probably due to an increased inhibition or reduced facilitation of their agonist drive.