1.
Jutberger, Hans, et al.
(författare)
Smoking Predicts Incident Fractures in Elderly Men : Mr OS Sweden
2010
Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 25:5, s. 1010-1016
Tidskriftsartikel (refereegranskat) abstract
The aim of the present study was to investigate the association between smoking and BMD, radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men, aged 69 - 80 years old from the Swedish Mr Os study, completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using DXA; 1412 men had an X-ray of the thoracic-/lumbar spine. Radiological registers were used to confirm reported new fractures after the baseline visit. At baseline 8.4 % were current smokers. Current smokers had 6.2 % lower BMD at the total hip and 5.4 % at the lumbar spine (p<0.001). Current smoking remained independently, inversely associated with BMD at the hip and lumbar spine after adjusting for age, height, weight, calcium intake, physical activity and centres as co-variates. Prevalent vertebral fractures among current smokers were increased in unadjusted analyses (OR 1.90; 95% CI: 1.26-2.87) and after adjustment for lumbar BMD (OR 1.67; 1.09-2.55). Smokers had a high risk for two or more prevalent vertebral fractures (OR 3.18; 1.88-5.36). During the average follow-up of 3.3 years, 209 men sustained an X-ray verified fracture. Incident fracture risk among smokers was calculated with Cox proportional hazard models. Current smokers had increased risk of all new fractures (HR 1.76; 1.19-2.61), non-vertebral osteoporotic fractures defined as humerus, radius, pelvis and hip fractures (HR 2.14; 1.18-3.88), clinical and X-ray verified vertebral fractures (HR 2.53; 1.37-4.65) as well as of hip fracture (HR 3.16; 1.44-6.95). After adjustment for BMD, including other co-variates, no significant association between smoking and incident fractures was found. Current tobacco smoking in elderly men is associated with low BMD, prevalent vertebral fractures and incident fractures, especially vertebral and hip fractures.
2.
3.
Nethander, Maria, 1980, et al.
(författare)
BMD-Related Genetic Risk Scores Predict Site-Specific Fractures as Well as Trabecular and Cortical Bone Microstructure
2020
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:4
Tidskriftsartikel (refereegranskat) abstract
CONTEXT: It is important to identify patients at highest risk of fractures. OBJECTIVE: To compare the separate and combined performances of bone-related genetic risk scores (GRSs) for prediction of forearm, hip and vertebral fractures separately, as well as of trabecular and cortical bone microstructure parameters separately. DESIGN, SETTING, AND PARTICIPANTS: Using 1103 single nucleotide polymorphisms (SNPs) independently associated with estimated bone mineral density of the heel (eBMD), we developed a weighted GRS for eBMD and determined its contribution to fracture prediction beyond 2 previously developed GRSs for femur neck BMD (49 SNPs) and lumbar spine BMD (48 SNPs). Associations between these GRSs and forearm (ncases = 1020; ncontrols = 2838), hip (ncases = 1123; ncontrols = 2630) and vertebral (ncases = 288; ncontrols = 1187) fractures were evaluated in 3 Swedish cohorts. Associations between the GRSs and trabecular and cortical bone microstructure parameters (n = 426) were evaluated in the MrOS Sweden cohort. RESULTS: We found that eBMDGRS was the only significant independent predictor of forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS were significant independent predictors of hip fractures. The eBMDGRS was the major GRS contributing to prediction of trabecular bone microstructure parameters while both FN-BMDGRS and eBMDGRS contributed information for prediction of cortical bone microstructure parameters. CONCLUSIONS: The eBMDGRS independently predicts forearm and vertebral fractures while both FN-BMDGRS and eBMDGRS contribute independent information for prediction of hip fractures. We propose that eBMDGRS captures unique information about trabecular bone microstructure useful for prediction of forearm and vertebral fractures. These findings may facilitate personalized medicine to predict site-specific fractures as well as cortical and trabecular bone microstructure separately.
4.
Manousaki, D., et al.
(författare)
Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis
2017
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 101:2, s. 227-238
Tidskriftsartikel (refereegranskat) abstract
Vitamin D insufficiency is common, correctable, and influenced by genetic factors, and it has been associated with risk of several diseases. We sought to identify low-frequency genetic variants that strongly increase the risk of vitamin D insufficiency and tested their effect on risk of multiple sclerosis, a disease influenced by low vitamin D concentrations. We used whole-genome sequencing data from 2,619 individuals through the UK10K program and deep-imputation data from 39,655 individuals genotyped genome-wide. Meta-analysis of the summary statistics from 19 cohorts identified in CYP2R1 the low-frequency (minor allele frequency = 2.5%) synonymous coding variant g.14900931G>A (p.Asp120Asp) (rs117913124[A]), which conferred a large effect on 25-hydroxyvitamin D (25OHD) levels (-0.43 SD of standardized natural log-transformed 25OHD per A allele; p value = 1.5 x 10(-88)). The effect on 25OHD was four times larger and independent of the effect of a previously described common variant near CYP2R1. By analyzing 8,711 individuals, we showed that heterozygote carriers of this low-frequency variant have an increased risk of vitamin D insufficiency (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.78-2.78, p = 1.26 3 10 x(-12)). Individuals carrying one copy of this variant also had increased odds of multiple sclerosis (OR = 1.4, 95% CI = 1.19-1.64, p = 2.63 3 10 x(-5)) in a sample of 5,927 case and 5,599 control subjects. In conclusion, we describe a low-frequency CYP2R1 coding variant that exerts the largest effect upon 25OHD levels identified to date in the general European population and implicates vitamin D in the etiology of multiple sclerosis.
5.
Estrada, Karol, et al.
(författare)
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
2012
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
Tidskriftsartikel (refereegranskat) abstract
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
6.
Justice, A. E., et al.
(författare)
Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
2017
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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.
7.
Andersson, Niklas, 1970, et al.
(författare)
Variants of the interleukin-1 receptor antagonist gene are associated with fat mass in men
2009
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 33:5, s. 525-533
Tidskriftsartikel (refereegranskat) abstract
Context: Immune functions seem to have connections to variations in body fat mass. Studies of knockout mice indicate that endogenous interleukin (IL)-1 can suppress mature-onset obesity. Objective: To systematically investigate our hypotheses that single- nucleotide polymorphisms (SNPs) and/or haplotypes variants in the IL-1 gene system are associated with fat mass. Subjects: The Gothenburg osteoporosis and obesity determinants (GOOD) study is a population-based cross-sectional study of 18-20 year-old men (n = 1068), from Gothenburg, Sweden. Major findings were confirmed in elderly men (n = 3014) from the Swedish part of the osteoporotic fractures in men (MrOS) multicenter population-based study. Main Outcome Measure: The genotype distributions and their association with body fat mass in different compartments, measured with dual-energy X-ray absorptiometry (DXA). Results: Out of 15 investigated SNPs in the IL-1 receptor antagonist (IL1RN) gene, a recently identified 30 untranslated region C4T (rs4252041, minor allele frequency 4%) SNP was associated with the primary outcome total fat mass (P = 0.003) and regional fat masses, but not with lean body mass or serum IL-1 receptor 1 (IL1RN) levels. This SNP was also associated with body fat when correcting the earlier reported IL1RN_2018 T4C (rs419598) SNP (in linkage disequilibrium with a well-studied variable number tandem repeat of 86 bp). The association between rs4252041 SNP and body fat was confirmed in the older MrOS population (P = 0.03). The rs4252041 SNP was part of three haplotypes consisting of five adjacent SNPs that were identified by a sliding window approach. These haplotypes had a highly significant global association with total body fat (P < 0.001). None of the other investigated members of the IL-1 gene family displayed any SNPs that have not been described previously to be significantly associated with body fat. Conclusions: The IL1RN gene, shown to enhance obesity by suppressing IL-1 effects in experimental animals, have no previously described gene polymorphisms and haplotypes that are associated with fat, but not lean mass in two populations of men. International Journal of Obesity (2009) 33, 525-533; doi: 10.1038/ijo.2009.47; published online 17 March 2009
8.
Rudäng, Robert, et al.
(författare)
Hip fracture prevalence in grandfathers is associated with reduced cortical cross-sectional bone area in their young adult grandsons
2010
Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:3, s. 1105-14
Tidskriftsartikel (refereegranskat) abstract
CONTEXT: Parent hip fracture prevalence is a known risk factor for osteoporosis. The role of hip fracture prevalence in grandparents on areal bone mineral density (aBMD) and bone size in their grandsons remains unknown. OBJECTIVE: The objective of the study was to examine whether hip fracture prevalence in grandparents was associated with lower aBMD and reduced cortical bone size in their grandsons. DESIGN AND SETTING: This was a population-based cohort study in Sweden. STUDY SUBJECTS: Subjects included 1015 grandsons (18.9 +/- 0.6) (mean +/- sd) and 3688 grandparents. MAIN OUTCOME MEASURES: aBMD, cortical bone size, volumetric bone mineral density and polar strength strain index of the cortex in the grandsons in relation to hip fracture prevalence in their grandparents were measured. RESULTS: Grandsons of grandparents with hip fracture (n = 269) had lower aBMD at the total body, radius, and lumbar spine, but not at the hip, as well as reduced cortical cross-sectional area at the radius (P
9.
10.
Atroshi, Isam, et al.
(författare)
Low calcaneal bone mineral density and the risk of distal forearm fracture in women and men: a population-based case-control study.
2009
Ingår i: Bone. - : Elsevier BV. - 1873-2763 .- 8756-3282. ; 45:4, s. 789-93
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE: We used dual X-ray absorptiometry (DXA) to measure calcaneal bone mineral density (BMD) and estimate the prevalence of osteoporosis in a population with distal forearm fracture and a normative cohort. METHODS: Patients 20 to 80 years of age with distal forearm fracture treated at one emergency hospital during two consecutive years were invited to calcaneal BMD measurement; 270 women (81%) and 64 men (73%) participated. A DXA heel scanner estimated BMD (g/cm(2)) and T-scores. Osteoporosis was defined as T-score< or =-2.5 SD. Of the fracture cohort, 254 women aged 40-80 years and 27 men aged 60-80 years were compared with population-based control cohorts comprising 171 women in the age groups 50, 60, 70 and 80 years and 75 men in the age groups 60, 70, and 80 years. RESULTS: In the fracture population no woman below 40 years or man below 60 years of age had osteoporosis. In women aged 40-80 years the prevalence of osteoporosis in the distal forearm fracture cohort was 34% and in the population-based controls was 25%; the age-adjusted prevalence ratio (PR) was 1.32 (95% CI 1.00-1.76). In the subgroup of women aged 60-80 years the age-adjusted prevalence ratio of osteoporosis was 1.28 (95% CI 0.95-1.71). In men aged 60-80 years the prevalence of osteoporosis in the fracture cohort was 44% and in the population-based controls was 8% (PR 6.31, 95% CI 2.78-14.4). The age-adjusted odds ratio for fracture associated with a 1-SD reduction in calcaneal BMD was in women aged 40-80 years 1.4 (95% CI 1.1-1.8), in the subgroup of women aged 60-80 years 1.2 (95% CI 0.95-1.6), and in men aged 60-80 years 2.6 (95% CI 1.7-4.1). Among those aged 60-80 years the area under the ROC curve was in women 0.56 (95% CI 0.49-0.63) and in men 0.80 (95% CI 0.70-0.80). CONCLUSIONS: The age-adjusted prevalence of osteoporosis based on calcaneal BMD is higher in individuals with distal forearm fracture than in population-based controls. BMD impairment is associated with increased odds ratio for forearm fracture in both women and men but the differences between cases and controls are more pronounced in men than in women, which may have implications in fracture prevention.
