Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78 , associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Multiple views detect more radiographic osteoarthritis than single views alone. When different combinations of views are used, the prevalence and compartmental distribution of osteoarthritis changes and this may alter the accepted relationship, or lack of it, between symptoms and radiographic change.

Mild isolated PF OA is significantly associated with symptoms of pain, stiffness and functional limitation. Further research on its recognition in clinical practice and the development of targeted treatments to prevent or slow progression are warranted.

Objectives: Joint pain and radiographic osteoarthritis are often discordant. Aim: To investigate this issue more closely by studying the detailed nature of pain and disability, and how this relates to radiographic osteoarthritis. Methods: Population-based study of 819 adults aged >50 years with knee pain. The severity of knee pain, stiffness and disability was measured using a validated scale (the Western Ontario and McMaster Universities (WOMAC) Score) and pain persistence was recorded. Global severity was measured by the graded chronic pain scale. Three radiographic views of the knees were obtained-weight-bearing posteroanterior metatarsophalangeal, supine skyline and supine lateral. Results: 745 participants with knee pain in the past 6 months were eligible (mean age 65 years, 338 men). Radiographic osteoarthritis was more common in those with a longer history and more persistent symptoms. A strong trend was found of radiographic osteoarthritis being more strongly associated with higher WOMAC scores for pain severity, stiffness and disability (adjusted odds ratio (95% confidence interval (CI)) for highest v lowest WOMAC category: 3.7 (2.0 to 6.7), 3.0 (2.0 to 4.6) and 2.8 (1.6 to 5.0), respectively). Those individual WOMAC items for pain and disability pertaining to weight-bearing mobility were the most strongly associated with radiographic osteoarthritis. Combining pain persistence and global severity, persistent severe pain was associated with a significant increase in the occurrence of radiographic osteoarthritis (2.6 (95% CI 1.5 to 4.7)). Conclusions: A consistent association was found between severity of pain, stiffness and physical function and the presence of radiographic osteoarthritis. This study highlights the potential contribution of underlying joint disease to the degree of pain and disability.

These results suggest a common sequence in the development of radiographic knee OA in symptomatic adults beginning in the PFJ, with subsequent addition and progression of TFJOA. It is proposed that isolated symptomatic PFJOA may be one marker for the future development of TFJOA and a target for the early management of knee OA.