Aims: To investigate work related and individual factors as predictors for incident neck pain among office employees working with video display units (VDUs). Methods: Employees in three administrative units of a medium sized city in Finland (n = 515) received mailed questionnaires in the baseline survey in 1998 and in the follow up survey in 1999. Response rate for the baseline was 81% (n = 416); respondents who reported neck pain for less than eight days during the preceding 12 months were included into the study cohort as healthy subjects (n = 232). The follow up questionnaire 12 months later was completed by 78% (n = 180). Incident neck cases were those reporting neck pain for at least eight days during the preceding 12 months. Results: The annual incidence of neck pain was 34.4% (95% CI 25.5 to 41.3). Poor physical work environment and poor placement of the keyboard increased the risk of neck pain. Among the individual factors, female sex was a strong predictor. Smoking showed a tendency for an increased risk of neck pain. There was an interaction between mental stress and physical exercise, those with higher mental stress and less physical exercise having especially high risk. Conclusion: In the prevention of neck disorders in office work with a high frequency of VDU tasks, attention should be given to the work environment in general and to the more specific aspects of VDU workstation layout. Physical exercise may prevent neck disorders among sedentary employees.T he evidence of risk factors for various types of neck disorders is based mostly on cross sectional studies, and a limited number of longitudinal studies. According to a recent review 1 and two later prospective studies, 2 3 a positive relation has been found between various neck disorders and work related risk factors, such as static neck and arm postures, duration of sitting, as well as workplace design. Among other job characteristics, high quantitative job demands, having little influence on one's work situation, and limited rest break opportunities have been found as predictors of neck pain. [4][5][6][7] Among individual factors, the role of psychological factors has been emphasised. 8 Concerning video display unit (VDU) work, the evidence of risk factors is based mainly on cross sectional studies. Increasing hours of computer use and incomplete work-rest cycle control, have been associated with musculoskeletal discomfort in the neck-shoulder area and upper extremities, 9-12 especially when using input devices, such as a keyboard or a mouse. [13][14][15] Computer use in sustained non-neutral postures, such as neck rotation and shoulder abduction, have been identified as risk factors for neck-shoulder symptoms.10 Postural stress caused by poor workstation ergonomics, such as inappropriate location of the screen, keyboard, or mouse, have been associated with musculoskeletal problems.11 [15][16][17][18][19] By ergonomic interventions, such as supporting the forearm on the tabletop, a reduction of postural load, 14 discomfort, 20 21 or neck pain 2...

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, non-coding variants from which pinpointing causal genes remains challenging. Here, we combined data from 718,734 individuals to discover rare and low-frequency (MAF<5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which eight in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2, ZNF169) newly implicated in human obesity, two (MC4R, KSR2) previously observed in extreme obesity, and two variants in GIPR. Effect sizes of rare variants are ~10 times larger than of common variants, with the largest effect observed in carriers of an MC4R stop-codon (p.Tyr35Ter, MAF=0.01%), weighing ~7kg more than non-carriers. Pathway analyses confirmed enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically-supported therapeutic targets to treat obesity.

Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70–0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FINRISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.