| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 4. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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| 5. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 6. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 7. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 8. |
- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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| 9. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 10. |
- Wain, Louise V, et al.
(författare)
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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets.
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:3, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10(-49)), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.
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| 11. |
- Yang, Jian, et al.
(författare)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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| 12. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 13. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 14. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 15. |
- Dempsey, P G, et al.
(författare)
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Influence on work pace conditions of temporal organization of work and rest
- 2006
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Ingår i: Meeting diversity in ergonomics.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A study was conducted to investigate the influence of different approaches to arranging the pace and temporal organization of repetitive assembly and disassembly tasks on variability in performance, and to compare assembly and disassembly times derived with psychophysical methods to more traditional Methods- Time Measurement (MTM) approaches. The conditions studied were a traditional assembly line arrangement where assemblies were started at a pace of 110 MTM, a batch condition where subjects were required to complete 36 assemblies in the amount of time based on 110 MTM, a line condition where subjects were required to take a break after every 6 assemblies requiring theffi to work at a 120 MTM pace, and a psychophysical condition where subjects were allowed to choose their pace.Overall, the results suggest that the mean times spent working remained fairly constant a cross conditions, with more variation in pauses in between cycles. For the second self-paced condition, subjects selected a significantly higher pace than 1 10 MTM, which was the basis for the other conditions. The higher pace was achieved through reduction in mean pauses, and the potential implications for musculoskeletal risk are discussed.
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| 16. |
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| 17. |
- Jackson, Jennie A, et al.
(författare)
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Identification of individual working styles in a long-cycle assembly task using kinematic and EMG variables
- 2016
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Konferensbidrag (refereegranskat)abstract
- Background.Increased motor variability while performing repetitive tasks has been suggested to decrease the risk of developing musculoskeletal disorders. However, support for this positive effect is lacking outside of short, simple, highly controlled tasks. It is also currently unknown whether or not existing motor variability metrics are viable for characterising occupational tasks. The purpose of this study was to assess motor variability during a long-cycle simulated occupational task. Using metrics previously validated for short-cycle tasks, this study aimed to determine the extent to which: (1) individuals dif-fered in motor variability with respect to kinematics and/or EMG activation; (2) individual motor variability was consistent across days; and (3) kinematics and EMG motor variability were correlated.Methods.Following a stringent, three-day training regime, 15 females proved sufficiently proficient to participate. On two occasions, participants performed 36 cycles of an assembly task (combining gross and fine motor skills) at 110 MTM pacing (51 s per cycle). For each cycle, multiple upper arm kinematic and trapezius EMG summary mean and SD variables were calculated; for each variable, the variability across the 36 cycles was assessed. The relative size of variability across individuals, and the consistency of each individual’s motor behaviour across days were assessed using kinematic and EMG vari-ables. The correlation between kinematic and EMG variables was also assessed.Results.Distinct individual behaviours were observed across days: some participants were clearly more consistent in their motor behaviour than others. Further, a high correlation was found between some kinematic and muscle activation variables.Discussion. Using previously validated upper arm assessment metrics, we were able to differentiate between individuals performing a long-cycle assembly task based on their degree of motor variability. Given the nature of our study task, we believe the metrics that we found to be successful at identifying individual behaviours could be used for assessing field tasks.
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| 18. |
- Jackson, Jennie A., et al.
(författare)
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Is what you see what you get? : Standard inclinometry of set upper arm elevation angles
- 2015
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Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 47, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Previous research suggests inclinometers (INC) underestimate upper arm elevation. This study was designed to quantify possible bias in occupationally relevant postures, and test whether INC performance could be improved using calibration. Participants were meticulously positioned in set arm flexion and abduction angles between 0 degrees and 150 degrees. Different subject-specific and group-level regression models comprising linear and quadratic components describing the relationship between set and INC-registered elevation were developed using subsets of data, and validated using additional data. INC measured arm elevation showed a downward bias, particularly above 600. INC data adjusted using the regression models were superior to unadjusted data; a subject-specific, two-point calibration based on measurements at 0 and 900 gave results closest to the 'true' set angles. Thus, inclinometer measured arm elevation data required calibration to arrive at 'true' elevation angles. Calibration to a common measurement scale should be considered when comparing arm elevation data collected using different methods.
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| 19. |
- Jackson, Jennie A., et al.
(författare)
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Observer performance in estimating upper arm elevation angles under ideal viewing conditions when assisted by posture matching software
- 2016
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Ingår i: Applied Ergonomics. - : Elsevier BV. - 0003-6870 .- 1872-9126. ; 55, s. 208-215
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Tidskriftsartikel (refereegranskat)abstract
- Selecting a suitable body posture measurement method requires performance indices of candidate tools. Such data are lacking for observational assessments made at a high degree of resolution. The aim of this study was to determine the performance (bias and between- and within-observer variance) of novice observers estimating upper arm elevation postures assisted by posture matching software to the nearest degree from still images taken under ideal conditions. Estimates were minimally biased from true angles: the mean error across observers was less than 2. Variance between observers was minimal. Considerable variance within observers, however, underlined the risk of relying on single observations. Observers were more proficient at estimating 0 and 90 postures, and less proficient at 60. Thus, under ideal visual conditions observers, on average, proved proficient at high resolution posture estimates; further investigation is required to determine how non-optimal image conditions, as would be expected from occupational data, impact proficiency.
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| 20. |
- Jackson, Jennie A, et al.
(författare)
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Occupational biomechanical risk factors for surgically treated ulnar nerve entrapment in a prospective study of male construction workers
- 2019
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Nordic Association of Occupational Safety and Health (NOROSH). - 0355-3140 .- 1795-990X. ; 45:1, s. 63-72
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to determine the association between occupational biomechanical exposures and occurrence of surgically treated ulnar nerve entrapment (UNE).Methods: A cohort of 229 689 male construction workers who participated in a national occupational health surveillance program (1971–1993) were examined prospectively over a 13-year case ascertainment period (2001–2013) for surgically treated UNE. Job title (construction trade), smoking status, height, weight and age were recorded on examination. Job titles were merged into occupational groups of workers performing similar work tasks and having similar training. Occupational biomechanical exposure estimates were assigned to each occupational group with a job exposure matrix (JEM) developed for the study. Negative binomial models were used to assess the relative risks for each biomechanical exposure and the sums of highly correlated biomechanical exposures. Surgical treatment of UNE was determined via a linkage with the Swedish Hospital Outpatient Surgery Register.Results: There were 555 cases of surgically treated UNE within the cohort. Workers exposed to forceful hand-grip factors had a 1.4-fold higher relative risk (95% CI 1.18–1.63) of undergoing surgical treatment for UNE compared to unexposed workers. Occupational groups comprising workers exposed to forceful hand-grip work showed the highest risks for UNE and included concrete workers, floor layers, ground preparatory workers, rock blasters, and sheet-metal workers.Conclusion: Forceful hand-grip work increases the risk for surgically treated ulnar nerve entrapment.
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| 21. |
- Lewis, Charlotte A., et al.
(författare)
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Occupational biomechanical risk factors for surgical treatment of subacromial impingement syndrome (SIS) in a 16-year prospective study among male construction workers
- 2019
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Ingår i: PREMUS 2019. ; , s. 165-165
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Shoulder disorders are common in the general population, with an annual prevalence up to over 40% per 1000 person-years. One common disorder is subacromial impingement syndrome (SIS), where a narrowing in the subacromial space causes compression of the tendons or bursa by the surrounding tissues. When conservative treatments are not effective, surgical treatments is often the alternative. The aim of the current study was to assess the association between occupational biomechanical exposures and the occurrence of surgically treated SIS in a large construction worker cohort over a 16-year follow-up period. Methods: A cohort of 280 747 male construction workers who participated in a national occupational health surveillance program (1971-1993) were examined prospectively (1987-2016) for SIS. SIS case status was defined by primary surgical treatment of diagnosis codes M75.1, M75.4, 726B, or 726C (ICD 10 and Swedish ICD 9 code systems), with data from the Swedish national registry for in- and out-patient surgery records. A job exposure matrix (JEM) was developed and biomechanical exposure estimates were assigned according to job title. Poisson regression models adjusted for age, BMI, smoking and a surgical time factor were used to estimate the relative risks (incidence rate ratios) of surgical treatment for SIS for each biomechanical factor.Results: There were 1381 cases in the cohort, which corresponded to an incidence rate of surgically treated SIS over the 16-year observation period of 46 cases per 100,000 person years. Increased risk for surgically treated SIS was shown for working with elevated arms (RR=1.27, 95% CI=1.02-1.58), heavy upper arm loads (RR=1.75, 95% CI=1.48-2.08), high grip force (RR=1.64, 95% CI=1.40-1.93), working with hand tools (RR=1.46, 95% CI=1.26-1.70), working with hand tools in a fixed posture (RR=1.28, 95% CI=1.14-1.44), and working with hand-arm vibration (RR=1.30, 95% CI=1.09-1.55).Conclusions: Working with elevated arms, high arm load, high grip force and vibrating handheld tools may increase the risk for SIS.
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| 22. |
- Lewis, Charlotte A., et al.
(författare)
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Surgery for subacromial impingement syndrome and occupational biomechanical risk factors in a 16-year prospective study among male construction workers
- 2023
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Ingår i: Scandinavian Journal of Work, Environment and Health. - Helsinki : NOROSH. - 0355-3140 .- 1795-990X. ; 49:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to assess the association between occupational biomechanical exposures and the occurrence of surgical treatment for subacromial impingement syndrome (SIS).Methods. A cohort of 220 295 male constructions workers who participated in a national occupational health surveillance program (1971–1993) were examined prospectively over a 16-year follow-up period (2001–2016) for surgically treated SIS. Worker job title, smoking status, height, weight, and age were registered on health examination. Job titles were mapped to 21 occupational groups based on tasks and training. A job exposure matrix (JEM) was developed with exposure estimates for each occupational group. Surgical cases were determined through linkage with the Swedish national in- and outpatient registers. Poisson regression was used to assess the relative risks (RR) for each biomechanical exposure.Results. The total incidence rate of surgically treated SIS over the 16-year observation period was 201.1 cases per 100 000 person-years. Increased risk was evident for workers exposed to upper-extremity loading (push/pull/lift) (RR 1.45–2.30), high hand grip force (RR 1.47–2.23), using handheld tools (RR 1.52–2.09), frequent work with hands above shoulders (RR 1.62–2.11), static work (RR 1.77–2.26), and hand-arm vibration (RR 1.78–2.13). There was an increased risk for SIS surgery for all occupational groups (construction trades) compared with white-collar workers (RR 1.56–2.61).Conclusions. Occupational upper-extremity load and posture exposures were associated with increased risk for surgical treatment of SIS, which underlines the need for reducing workplace exposures and early symptom detection in highly exposed occupational groups.
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| 23. |
- Repapi, Emmanouela, et al.
(författare)
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Genome-wide association study identifies five loci associated with lung function.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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