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| 33. |
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| 34. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 35. |
- Cronholm, Felix, et al.
(författare)
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The fracture predictive ability of a musculoskeletal composite score in old men - data from the MrOs Sweden study
- 2019
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Ingår i: BMC Geriatr. - : Springer Science and Business Media LLC. - 1471-2318. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDetection of high-risk individuals for fractures are needed. This study assessed whether level of physical activity (PA) and a musculoskeletal composite score could be used as fracture predictive tools, and if the score could predict fractures better than areal bone mineral density (aBMD).MethodsMrOs Sweden is a prospective population-based observational study that at baseline included 3014 men aged 69-81years. We assessed femoral neck bone mineral content (BMC), bone area, aBMD and total body lean mass by dual energy X-ray absorptiometry, calcaneal speed of sound by quantitative ultrasound and hand grip strength by a handheld dynamometer. PA was assessed by the Physical Activity Scale for the Elderly (PASE) questionnaire. We followed the participants until the date of first fracture, death or relocation (median 9.6years). A musculoskeletal composite score was calculated as mean Z-score of the five measured traits. A Cox proportional hazards model was used to analyze the association between the musculoskeletal traits, the composite score and incident fractures (yes/no) during the follow-up period. Data are presented as hazard ratios (HR) with 95% confidence intervals (95% CI) for fracture for a+1 standard deviation (SD) change (+1 Z-score) in the various musculoskeletal traits as well as the composite score. We used a linear regression model to estimate the association between level of PA, measured as PASE-score and the different musculoskeletal traits as well as the composite score.ResultsA+1 SD higher composite score was associated with an incident fracture HR of 0.61 (0.54, 0.69), however not being superior to aBMD in fracture prediction. A+1 SD higher PASE-score was associated with both a higher composite score and lower fracture incidence (HR 0.83 (0.76, 0.90)).ConclusionsThe composite score was similar to femoral neck aBMD in predicting fractures, and also low PA predicted fractures. This highlights the need of randomized controlled trials to evaluate if PA could be used as a fracture preventive strategy.
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| 36. |
- Cöster, Marcus E., et al.
(författare)
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Physical function tests predict incident falls : A prospective study of 2969 men in the Swedish Osteoporotic Fractures in Men study
- 2020
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 48:4, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Falls are common in the elderly population, and fall-related injuries are a major health issue. We investigated the ability of simple physical tests to predict incident falls. Methods: The Swedish Osteoporotic Fractures in Men (MrOS) study includes 3014 population-based men aged 69–81 years at the start of the study. These men performed five different physical tests at baseline: right-hand grip strength, left-hand grip strength, timed stand test, 6 m walking test (time and steps) and narrow walking test. During the first study year, we asked participants to fill out questionnaires regarding falls 4, 8 and 12 months after baseline. A total of 2969 men completed at least one questionnaire and were included in this study. We used generalised estimating equations and logarithmic regression models to estimate odds ratios for fallers and recurrent fallers (more than one fall during the one-year examination period) in each quartile of men for each physical test. Results: The proportions of fallers and recurrent fallers were higher in the lowest quartile of the physical tests than in the other three quartiles combined for all physical tests. A reduction of one standard deviation in respective physical test resulted in a 13–21% higher risk of becoming a faller and a 13–31% higher risk of becoming a recurrent faller. Conclusions: Low results on simple physical tests is a risk factor for incident falls in elderly Swedish men and may facilitate identification of high-risk individuals suitable for fall-intervention programs.
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| 37. |
- Darelid, Anna, et al.
(författare)
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Bone turnover markers predict bone mass development in young adult men: a five-year longitudinal study.
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:4, s. 1460-8
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Tidskriftsartikel (refereegranskat)abstract
- Peak bone mass is an important factor for the lifetime risk of developing osteoporosis. Ways to predict bone development in young adulthood are lacking. Objective and Main Outcome Measures: The aim of this study was to investigate whether baseline measurements of bone turnover markers could predict bone development in early adulthood in men.
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| 38. |
- Darelid, Anna, et al.
(författare)
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Catch up in bone acquisition in young adult men with late normal puberty.
- 2012
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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. ; 27:10, s. 2198-2207
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the development of bone mineral density (BMD) and content (BMC) in relation to peak height velocity (PHV), and to investigate whether late normal puberty was associated with remaining low BMD and BMC in early adulthood in men. In total, 501 men (18.9±0.5 (mean±SD) yrs at baseline) were included in this five-year longitudinal study. Areal BMD (aBMD) and BMC, volumetric BMD (vBMD) and cortical bone size were measured using DXA and pQCT. Detailed growth and weight charts were used to calculate age at PHV, an objective assessment of pubertal timing. Age at PHV was a strong positive predictor of the increase in aBMD and BMC of the total body (R(2) aBMD 11.7%;BMC 4.3%), radius (R(2) aBMD 23.5%;BMC 22.3%), and lumbar spine (R(2) aBMD 11.9%;BMC 10.5%) between 19 and 24 yrs (p<0.001). Subjects were divided into three groups according to age at PHV (early, middle and late). Men with late puberty gained markedly more in aBMD and BMC at the total body, radius and lumbar spine, and lost less at the femoral neck (p<0.001) than men with early puberty. At age 24, no significant differences in aBMD or BMC of the lumbar spine, femoral neck, or total body were observed, while a deficit of 4.2% in radius aBMD, but not in BMC, was seen for men with late vs. early puberty (p<0.001). PQCT measurements of the radius at follow-up demonstrated no significant differences in bone size, whereas cortical and trabecular vBMD were 0.7% (p<0.001) and 4.8% (p<0.05) lower in men with late vs. early puberty. In conclusion, our results demonstrate that late puberty in males was associated with a substantial catch up in aBMD and BMC in young adulthood, leaving no deficits of the lumbar spine, femoral neck or total body at age 24.
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| 39. |
- Darelid, Anna, et al.
(författare)
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Trabecular Volumetric Bone Mineral Density is Associated With Previous Fracture During Childhood and Adolescence in Males - The GOOD Study.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:3, s. 537-44
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Areal bone mineral density (aBMD) measured with dual X-ray absorptiometry (DXA) has been associated with fracture risk in children and adolescents, but it remains unclear whether this association is due to volumetric BMD (vBMD) of the cortical and/or trabecular bone compartments or the bone size. The aim of this study was to determine whether vBMD or bone size was associated with x-ray verified fractures in men during growth. In total, 1068 men (age 18.9+/-0.6 yrs), were included in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study. Areal BMD was measured by DXA, while cortical and trabecular vBMD and bone size were measured by peripheral quantitative computerized tomography (pQCT). X-ray records were searched for fractures. Self reported fractures in 77 men could not be confirmed in these records. These men were excluded, resulting in 991 included men, of which 304 men had an x-ray verified fracture and 687 were non-fracture subjects. Growth charts were used to establish the age of peak height velocity (PHV, n=600). Men with prevalent fractures had lower aBMD (lumbar spine 2.3%, p=0.005; total femur 2.6%, p=0.004, radius 2.1%, p<0.001) at all measured sites than men without fracture. Using pQCT measurements, we found that men with a prevalent fracture had markedly lower trabecular vBMD (radius: 6.6 %, p=7.5x10(-8); tibia: 4.5 %, p=1.7x10(-7)) as well as slightly lower cortical vBMD (radius: 0.4 %, p=0.0012; tibia: 0.3 %, p=0.015), but not reduced cortical cross sectional area, than men without fracture. Every SD decrease in trabecular vBMD of the radius and tibia was associated with 1.46 (radius CI 1.26-1.69 (95% CI); tibia CI 1.26-1.68) times increased fracture prevalence. The peak fracture incidence coincided with the timing of PHV (+/-1 year). In conclusion, trabecular vBMD, but not aBMD, was independently associated with prevalent x-ray verified fractures in young men. Further studies are needed to determine if assessment of trabecular vBMD could enhance prediction of fractures during growth in males.
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