| 21. |
- Jiang, X., et al.
(författare)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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| 22. |
- Johansson, Helena, 1981, et al.
(författare)
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Is the Swedish FRAX model appropriate for Swedish immigrants?
- 2015
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 26:11, s. 2617-2622
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population born in Sweden. Thus, the use of a FRAXA (R) model in immigrants overestimates the risk of fracture, and the use of country of origin-specific models may be more appropriate. Introduction Age-specific fracture and mortality rates vary between countries so that FRAX tools are country-specific. In the case of immigrants, it is not known whether the model for the original or the new country is most appropriate. The aim of this study was to compare the incidence of hip fractures in foreign-born and Swedish-born individuals residing in Sweden. Methods We studied the incidence of hip fracture in all men and women aged 50 years or more in Sweden between 1987 and 2002. The population comprised 2.8 million Swedish-born and 270,000 foreign-born individuals. Results Incident hip fractures occurred in 239,842 Swedish-born and 12,563 foreign-born individuals. The hip fracture incidence rose with age for both groups and was higher for women than men amongst both Swedish-born and foreign-born individuals. The hip fracture incidence for the Swedish-born cohort was approximately twice that of immigrants. For example, at the age of 70 years, the annual hip fracture incidence (per 100,000) was 450 (95 % CI 446-454) for a Swedish-born woman and 239 (95 % CI 223-257) for a foreign-born woman at the time of immigration. The hip fracture incidence rose slowly with time from immigration (0.6 % per annum, 95 % CI 0.5-0.8 %) but remained significantly lower than for Swedish-born individuals even after 40 years of residence. Conclusions The incidence of hip fracture in Sweden is substantially lower in immigrants than in the population native to Sweden. Although there was a small rise in age- and sex-specific incidence after immigration, the incidence remained markedly lower than that observed in Swedish-born individuals. Thus, the use of a FRAX model for Sweden will overestimate the risk of fracture for foreign-born individuals living in Sweden.
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| 23. |
- Johansson, Helena, 1981, et al.
(författare)
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Low risk for hip fracture and high risk for hip arthroplasty due to osteoarthritis among Swedish farmers
- 2018
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:3, s. 741-749
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden. Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty. Introduction The risks of hip fracture and hip arthroplasty are influenced by factors including socioeconomic status, education, urbanization, latitude of residence, and physical activity. Farming is an occupation encompassing rural living and high level of physical activity. Therefore, we aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden. Methods We studied the risk of hip fracture, and hip arthroplasty due to primary osteoarthritis, in all men and women aged 35 years or more in Sweden between 1987 and 2002. Documented occupations were available in 3.5 million individuals, of whom 97,136 were farmers. The effects of age, sex, income, education, location of residence, and occupation on risk of hip fracture or hip arthroplasty were examined using a modification of Poisson regression. Results A total of 4027 farmers and 93,109 individuals with other occupations sustained a hip fracture, while 5349 farmers and 63,473 others underwent a hip arthroplasty. Risk of hip fracture was higher with greater age, lower income, lower education, higher latitude, and urban area for all men and women. Compared to all other occupations, male farmers had a 20% lower age-adjusted risk of hip fracture (hazard ratio (HR) 0.80, 95% CI 0.77-0.84), an effect that was not seen in female farmers (HR 0.96, 95% CI 0.91-1.01). Both male and female farmers had a higher age-adjusted risk for hip arthroplasty. Conclusions Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty.
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| 24. |
- Johansson, Lena, 1972, et al.
(författare)
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Decreased physical health-related quality of life—a persisting state for older women with clinical vertebral fracture
- 2019
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Ingår i: Osteoporosis International. - London : Springer London. - 0937-941X .- 1433-2965. ; 30:10, s. 1961-1971
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study of older Swedish women, we investigated if clinical vertebral fracture was associated with lower health-related quality of life (HRQoL) and determined whether the association remained over time. Clinical vertebral fracture was associated with lower HRQoL and the effect persisted for up to 18.9 years.IntroductionVertebral fractures are often associated with back pain and reduced physical function, which might result in isolation and depression. As a result, women with vertebral fractures often have lower health-related quality of life (HRQoL), but during what time frame the decrease lingers is unclear. Therefore, the aim of this study was to investigate if clinical vertebral fracture and hip fracture were associated with lower HRQoL and to determine whether the associations remained over time.MethodsVertebral fracture assessments (VFA) were performed using dual-energy X-ray absorptiometry. Data regarding prior fractures, medications, medical history, and physical activity was collected using a questionnaire. Self-rated physical HRQoL was assessed using the 12-Item Short-Form Health Survey (SF-12). Women with clinical vertebral fractures were divided into tertiles according to time since fracture onset and their HRQoL was compared with non-fractured women.ResultsIn a population-based cross-sectional study of 3028 women aged 77.8 ± 1.63 (mean ± SD), a total of 130 (4.3%) women reported at least one clinical vertebral fracture. Women with a clinical vertebral fracture, divided into tertiles (T1–T3) depending on time since the fracture occurred, had lower HRQoL (T1: 36.3 ± 10.8; T2: 41.0 ± 9.94; and T3:41.6 ± 11.4) than women without fracture (46.2 ± 10.6; p < 0.001). Using linear regression analysis, clinical vertebral fracture was associated with reduced physical HRQoL for up to 18.9 years, independently of covariates (age, height, weight, smoking, prior stroke, mental HRQoL, grip strength, and lumbar spine BMD).ConclusionsClinical vertebral fracture was associated with lower self-rated physical HRQoL, for up to 18.9 years after time of fracture. © 2019, The Author(s).
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| 25. |
- Johansson, Lisa, et al.
(författare)
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The Prevalence of Vertebral Fractures Is Associated With Reduced Hip Bone Density and Inferior Peripheral Appendicular Volumetric Bone Density and Structure in Older Women
- 2018
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 1523-4681. ; 33:2, s. 250-260
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Tidskriftsartikel (refereegranskat)abstract
- Vertebral fractures (VFs) are among the most severe and prevalent osteoporotic fractures. Their association with bone microstructure have been investigated in several retrospective case-control studies with spine radiography for diagnosis of VF. The aim of this population-based cross-sectional study of 1027 women aged 75 to 80 years was to investigate if prevalent VF, identified by vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA), was associated with appendicular volumetric bone density, structure, and bone material strength index (BMSi), independently of hip areal bone mineral density (aBMD). aBMD was measured using DXA (Discovery; Hologic); BMSi with microindentation (Osteoprobe); and bone geometry, volumetric BMD, and microstructure with high-resolution peripheral quantitative computed tomography (HRpQCT) (XtremeCT; Scanco Medical AG). aBMD was lower (spine 3.2%, total hip [TH] 3.8%) at all sites in women with VF, but tibia BMSi did not differ significantly compared to women without VF. In multivariable adjusted logistic regression models, radius trabecular bone volume fraction and tibia cortical area (odds ratio [OR] 1.26; 95% confidence interval [CI], [1.06 to 1.49]; and OR 1.27 [95% CI, 1.08 to 1.49], respectively) were associated with VF prevalence, whereas BMSi and cortical porosity were not. The risk of having one, two, or more than two VFs was increased 1.27 (95% CI, 1.04 to 1.54), 1.83 (95% CI, 1.28 to 2.61), and 1.78 (95% CI, 1.03 to 3.09) times, respectively, for each SD decrease in TH aBMD. When including either cortical area, trabecular bone volume fraction or TBS in the model together with TH aBMD and covariates, only TH aBMD remained independently associated with presence of any VF. In conclusion, TH aBMD was consistently associated with prevalent VFA-verified VF, whereas neither trabecular bone volume fraction, cortical area, cortical porosity, nor BMSi were independently associated with VF in older women. © 2017 American Society for Bone and Mineral Research.
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| 26. |
- Johansson, Lisa, et al.
(författare)
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Vertebral fractures and their association with health-related quality of life, back pain and physical function in older women.
- 2018
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965. ; 29:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Studies investigating prevalent vertebral fracture (VF) diagnosed using densitometry-based VF assessment (VFA) and associations with physical function, assessed by performance-based measures, are lacking. In this population-based study of 1027 older women, we found that prevalent VF, identified by VFA, was associated with inferior physical health, back pain and inferior physical function.Several studies have investigated the associations between health-related quality of life (HRQL) and back pain with prevalent VF, detected by spine radiographs, but just a few have been population-based and have used vertebral fracture assessment (VFA) for diagnosing VF. The aims of this study were to investigate associations between prevalent VF, detected by VFA, with HRQL, back pain and physical function, and investigate if also mild VFs were associated with these clinical parameters.One thousand twenty-seven women aged 75-80years participated in this population-based cross-sectional study. VF was identified by VFA using dual-energy X-ray absorptiometry. HRQL was assessed by SF-12, back pain during the past 12months using a questionnaire, and physical function was tested with one leg standing (OLS), Timed Up and Go (TUG), walking speed, 30-s chair stand test and maximum grip strength.Physical health (Physical Component Summary, PCS), derived from SF-12, was worse (43.5±11.3 vs. 46.2±10.5, p<0.001) and back pain more frequent in women with any VF than in women without (69.0 vs. 59.9%, p=0.008). PCS and physical function (OLS, 30-s chair stand test), were significantly worse for mild VF compared to no VF (43.8±10.9 vs. 46.2±10.5, p<0.001, 12.7±9.9 vs. 15.3±10.4s, p=0.038, 10.7±3.2 vs. 11.4±3.4 times, p=0.021, respectively). In multivariable adjusted linear regression models, VF prevalence was associated with PCS (β=-0.079, p=0.007), TUG (β=0.067, p=0.021), walking speed (β=-0.071, p=0.009) and 30-s chair stand test (β=-0.075, p=0.012).In conclusion, prevalent VF, diagnosed by VFA, was associated with inferior physical health, back pain and inferior physical function, indicating VFA is useful for diagnosing clinically relevant vertebral fractures. Also, mild VF was associated with inferior physical health and inferior physical function.
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| 27. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 28. |
- Karasik, D., et al.
(författare)
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Disentangling the genetics of lean mass
- 2019
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 109:2, s. 276-287
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
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| 29. |
- Karlsson, M. K., et al.
(författare)
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Characteristics of Prevalent Vertebral Fractures Predict New Fractures in Elderly Men
- 2016
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Ingår i: Journal of Bone and Joint Surgery-American Volume. - : Ovid Technologies (Wolters Kluwer Health). - 0021-9355 .- 1535-1386. ; 98:5, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have shown that specific characteristics of prevalent vertebral fractures are associated with a markedly low bone mineral density. This study evaluates if these characteristics also predict subsequent fractures. Methods: MrOS (Mister Osteoporosis) Sweden is a population-based, prospective observational study that includes 3014 community-living men who are sixty-nine to eighty-one years of age. At baseline, 1453 men underwent lateral thoracic and lumbar spine radiography; radiographs of 1427 men were readable. A radiologist identified and characterized prevalent vertebral fractures. Incident fractures during the next five and ten years were objectively registered with use of radiographs. The annual fracture incidence and relative risk of sustaining new fractures were assessed for men with and without baseline prevalent vertebral fracture. Data are presented as the mean and the 95% confidence interval. Results: There were 215 men (15.1%) with at least one prevalent vertebral fracture. During the five-year follow-up, these men had a relative risk of 3.3 (95% confidence interval, 2.6 to 4.3) of sustaining new fractures. The relative risk of sustaining any fracture was especially high in men with two or more prevalent vertebral fractures at 5.5 (95% confidence interval, 3.7 to 7.8), in men with different types of prevalent vertebral fractures at 5.7 (95% confidence interval, 3.6 to 8.5), in men with prevalent fractures in both the thoracic and lumbar regions at 6.4 (95% confidence interval, 4.5 to 8.8), and in men with prevalent fractures with a degree of vertebral body compression in the three worst quartiles, with the relative risk for the worst quartile at 4.0 (95% confidence interval, 2.6 to 5.9). Conclusions: Older men with a prevalent vertebral fracture have three times increased risk of sustaining new fractures compared with men without a vertebral fracture. Older men with two or more prevalent vertebral fractures, different types of fractures (wedge, biconcave, and/or crush), fractures in both the thoracic and lumbar regions, and a degree of vertebral body compression in the three worst quartiles are at an especially high risk of sustaining new fractures. Older men with prevalent vertebral fractures should be considered for fracture-prevention efforts.
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| 30. |
- Karlsson, Magnus K, et al.
(författare)
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Characteristics of Prevalent Vertebral Fractures Predict New Fractures in Elderly Men.
- 2016
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Ingår i: Journal of Bone and Joint Surgery. American Volume. - 1535-1386. ; 98:5, s. 379-385
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Tidskriftsartikel (refereegranskat)abstract
- Studies have shown that specific characteristics of prevalent vertebral fractures are associated with a markedly low bone mineral density. This study evaluates if these characteristics also predict subsequent fractures.
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