SummaryBackgroundOsteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity.MethodsWe undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11 009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42 938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent.FindingsWe identified five genome-wide significant loci (binomial test p≤5·0×10−8) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08–1·16]; p=7·24×10−11), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight—a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects.InterpretationOur findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.FundingarcOGEN was funded by a special purpose grant from Arthritis Research UK.

Consumption of an adequate volume of high-quality colostrum is vital to a dairy calf's ability to survive and become a productive herd member. However, some dairy herds have reported a deficiency of colostrum production, which ranges from a low volume to no colostrum produced, by cows during fall and winter. Little information regarding this phenomenon exists. The purpose of this study was to characterize the syndrome and identify potential risk factors for low colostrum yield. A 2,500-cow Jersey dairy farm was enrolled in a prospective cohort study in May 2016, to evaluate possible effects of photoperiod, temperature, and cow factors on colostrum production. Dairy personnel were trained to collect, weigh, and evaluate colostrum quality. Information on parity, previous lactation length, previous 305-d mature-equivalent milk production, and dry period length were collected through the farm's dairy management software. Weather and photoperiod data were also collected. Over the year of enrollment, 2,988 eligible cows calved and had colostrum weights recorded and 38% were primiparous (n = 1,143), 25% were in their second lactation (n = 752), and 37% were in their third or greater lactation (n = 1,093). The overall average colostrum yield was 6.6 kg/cow in June 2016, 2.5 kg/cow in December 2016, and 4.8 kg/cow in May 2017. Multiparous cows had a larger decline in colostrum production between June and December (6.6 to 1.3 kg/cow) compared with primiparous animals (6.5 to 4.2 kg/cow). Overall, average colostrum production decreased by 0.17 kg/cow per week during this time, 0.22 kg for multiparous cows and 0.08 kg for primiparous cows. A logistic regression model was constructed for all cows to evaluate effects of cow factors on low colostrum production (<2.7 kg at first milking). Dry period length, calf sex, singleton or twin, age at freshening, month of calving and previous lactation length were significantly associated with the probability of low colostrum yield (<2.7 kg at first milking). A cross-correlation function analysis between the time series for colostrum yield and photoperiod revealed a high correlation at the time of calving and 1 mo prior, particularly for multiparous cows. A pedigree analysis showed that extreme colostrum yield (low vs. high) followed some sire lines. Low colostrum production in this herd could have an economic effect on the dairy and calf health and appears to have a strong seasonal and, potentially, a genetic component.

Detection of lameness in individual cows is important for the prompt treatment of this painful and production-limiting disease. Current methods for lameness detection involve watching cows walk for several strides. If clinical signs predictive of lameness could be observed more conveniently, as cows are undergoing regularly scheduled examinations while standing, detection levels could increase. The objective of this study was to assess the association between postures observed while cows are standing in stanchions and clinical lameness evaluated by locomotion scoring, and to evaluate the observation of these postures as a test for lameness. The study included 1,243 cows from 4 farms. Cows were observed while standing in stanchions for regularly scheduled management procedures and the presence of arched back and cow-hocked, wide-stance, and favored-limb postures were recorded. The same cows were locomotion-scored as they exited the milking parlor. The proportion of cows observed with arched back and cow-hocked and favored-limb postures increased with increasing severity of lameness (higher locomotion score) but did not increase for the wide-stance posture. For the presence of these postures as a test for lameness (locomotion score ≥3), sensitivity and specificity were 0.63 and 0.64 for back arch, 0.54 and 0.57 for cow hocks, and 0.05 and 0.98 for favored limb. Back-arched, cow-hocked, and favored limb postures were associated with lameness but were not highly sensitive or specific as diagnostic tests. However, observation of back arch may be useful to identify cows needing further examination.

Monitoring herd lameness prevalence has utility for dairy producers and veterinarians in their efforts to reduce lameness, for animal welfare assessment programs, and for researchers. Locomotion scoring is a method used to quantify lameness and calculate prevalence. Because of the time necessary to locomotion score each cow in large dairy herds, a sampling strategy to determine herd lameness prevalence that allows scoring of fewer cows would be useful. Such a sampling strategy must be validated for accuracy compared with the lameness prevalence when all cows in a herd are locomotion scored. The purpose of this study was to assess 3 previously suggested methods of estimating lameness prevalence by strategic sampling of dairy herds. Sampling strategies tested included (1) sampling a calculated number of cows in the middle third of the milking parlor exit order for each pen, (2) sampling a calculated number of cows weighted across pens and distributed evenly within each pen, and (3) sampling all cows in the high production, low production, and hospital pens. Lactating cows on 5 dairy farms in Washington and Oregon (n=4,422) were locomotion scored using a 5-point scale to determine herd-level lameness prevalence (percentage with locomotion score ≥3). Milking parlor exit order, order in headlocks at the feed bunk within each pen, and breed were recorded for each cow. The number of days in lactation, milk production, and parity were collected from farm computer records. Pen grouping strategy for each farm was obtained by interview with farm management. Sampling strategies were modeled using the locomotion score data set for each herd. Estimates of lameness prevalence obtained from the milking parlor exit order sample and the sample distributed across pens were within 5 percentage points of the whole herd prevalence. The third strategy estimated the lameness prevalence within 5 percentage points on 4 farms, but overestimated prevalence on 1 farm. Pen-level prevalence obtained by locomotion score of all cows in the pen was variable and not reliably predictive of herd-level prevalence. Cows of Holstein breed, parity >1, and exiting the milking parlor in the last 20% of the pen had greater odds of lameness compared with other breeds, parities, and milking parlor exit order groups in a multivariate analysis. This study indicates that the sampling strategies using the middle of milking parlor exit order and a calculated sample distributed across the herd may be used to obtain an estimate of herd lameness prevalence.

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