Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Musculoskeletal pain and physical functioning in the oldest old.

BACKGROUND: Little is known about the impact of pain on physical functioning among the oldest-old subjects. In this study, we first examined the associations between the number of painful sites and measures of physical functioning reflecting different stages of the disablement process (physical impairment, functional limitation and disability) among nonagenarians (more than ninety years old persons). Second, we described the effect of painful sites on disability during a 2-year follow-up period. METHODS: This study is based on baseline (n = 1177) and 2-year follow-up (n = 709) data of the nationwide Danish 1905 cohort study. Musculoskeletal pain was assessed as reported pain in back, hips or knees when moving or resting. Physical performance measures included maximum grip strength and habitual walking speed. Disability in performing activities of daily living was defined as the need for assistive device or personal help in transferring, dressing, washing, using toilet and/or walking indoors. RESULTS: At baseline, the number of painful sites was significantly associated with measured grip strength and walking speed as well as self-reported disability in a stepwise manner; the more sites with pain, the poorer the physical functioning. The follow-up analyses showed corresponding but slightly weaker stepwise associations between baseline pain and disability level at follow-up, and indicated that although on the whole, single or multi-site pain did not predict the onset of disability, multi-site pain increased the risk of developing severe disability. CONCLUSIONS: The findings of this study suggest that musculoskeletal pain in nonagenarians is highly prevalent and is associated with poor physical performance and disability.

Genetic variants in the choline acetyltransferase (ChAT) gene are modestly associated with normal cognitive function in the elderly.

Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested the importance of genetic variants in the ChAT gene in normal cognitive function of elderly in a study sample of Danish twins and singletons (N = 2070). The ChAT rs3810950 A allele, which has been associated with increased risk for AD, was found to be associated with a decrease cognitive status evaluated by a five-component cognitive composite score [P = 0.03, regression coefficient -0.30, 95% confidence interval (CI) -0.57 to -0.02], and the rs3810950 and rs8178990 ancestral GC haplotype was also associated with better cross-sectional cognitive composite score (P = 0.04, regression coefficient 0.59, 95% CI 0.03 to 1.16). Growth curve model analyses applied to up to 10 years of follow-up data showed that the rs3810950 A allele was associated with a lower cognitive composite score and Mini Mental State Examination at the lowest age (73 years of age), and was lower in the whole interval 73-82 although the absolute difference became smaller with age. Stratification by the presence of the APOE ε4 allele showed that rs3810950 AG/non-APOE ε4 carriers and rs3810950 AA/APOE ε4 carriers were associated with a lower cognitive composite score in younger elderly 73-83 years of age, similar to previous reports of association with AD.