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- Khalili, Bita, et al.
(författare)
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Associations between common genetic variants and income provide insights about the socioeconomic health gradient
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EA's genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
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| 3. |
- Penno, Hendrik, 1962-, et al.
(författare)
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Polymorphic variations in the gene for osteoprotegerin are associated with bone mineral density and predict fractures in elderly men: Data from Mr OS Sweden. :
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Osteoporosis is a polygenetic disorder where several genes are known to be involved. In this report we investigated the association between polymorphic variations in the gene for osteoprotegerin (OPG) and bone mineral density (BMD) and fragility fractures in elderly men. Methods: The study was performed in Mr OS Sweden, a cohort consisting of 3014 randomly selected men between 69 and 81 years of age, where at baseline BMD was measured at hip and spine by dual energy X ray absorbtiometry (DXA) and blood samples extracted. DNA was then isolated and the OPG gene was characterised. Prospective fractures, all verified by X-rays, were recorded for 5 years following baseline. Common variants in the 3’ and 5’UTR of the OPG gene was typed using Sequenom technology. Results: There was a significant association between common genetic variants in the gene for OPG and BMD at both hip (top SNP rs10955908, p<0.0008) and spine (top SNP rs10955908, p<0.0008) . The differences in BMD related to presence of various OPG alleles were between 0.5-3.5%. There was also an association with fragility fractures with odds ratio for rs6993813 reaching statistical significance (p=0.03) For five other SNPs were tested were the association with fractures did not reach statistical significance (p=0.12 - 0.19). Conclusion: Polymorphic variations in the gene for OPG are associated with BMD and fragility fractures in elderly men. The data support the view that variation in the OPG gene is a determinant for BMD and fragility fracture risk also in men.
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| 4. |
- Penno, Hendrik, 1962-, et al.
(författare)
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Polymorphic variations in the gene for osteoprotegerin do not predict prostate cancer incidence: Data from MrOS Sweden.
- 2011
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background Prostate cancer cells have been shown to produce and secrete osteoprotegerin (OPG), that inhibits tumor cell death by binding to TNF-related anti apoptotic ligand (TRAIL), and also is a key regulator of bone turnover . Bone metastases play a central role in prostate cancer spreading. However, the mechanisms underlying the interaction between bone cells and prostate cancer cells are not known. The aim of this study was therefore to investigate whether polymorphic variations in the gene for OPG affect prostate cancer incidence, or extra prostatic disease and metastasis. Methods The study was performed in the MrOS-Sweden cohort consisting of 3,014 men aged 69-81 years. DNA was collected at the start of the study and the gene for OPG was investigated concerning SNPs previously shown to regulate bone mineral density (BMD), and therefore of biological importance. Data on prostate cancer prevalence at baseline, and incidence during a 3-year follow-up were collected from the Swedish Cancer Register. The association of six OPG polymorphisms with prostate cancer was evaluated. Results The association between six OPG polymorphisms and prostate cancer was evaluated. In these analyses there were no significant genotype differences between prostate cancer patients and controls. A tendency for an association between OPG genotypes and more severe disease (p=0.08-0.09) was found however regarding OPG genotypes. Conclusion Polymorphic variations in the gene for OPG are not associated with prostate cancer incidence. Our data on staging of prostate cancer at the diagnose according to the TNM system in regard to the variations in the OPG gene gave some tendencies to possible involvement but further studies are required to investigate the potential role of the OPG/RANK/RANKL system in the metastatic skeletal prostate cancer spreading, and growth, in bone.
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| 5. |
- Siilin, Helene, et al.
(författare)
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Associations of primary hyperparathyroidism and physical performance, fall- and fracture risk in elderly men - Mr Os Sweden : PHPT-physical performance, falls and fractures in elderly men
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Primary hyperparathyroidism (PHPT) is an endocrine disease associated with deterioration of the skeleton and neuromuscular dysfunction. This study has explored associations between PHPT, physical function and risk of falls and fractures in elderly men. Method: Serum parameters of calcium homeostasis, physical testing of neuromuscular function (grip strength, time stands, 6 meters walking and 20 cm narrow walking tests), self reported falls during 12 months preceding the testing and self reported fractures were evaluated in 3014 men aged 69 to 81 years in the MrOS Sweden cohort. Subjects were diagnosed with PHPT (n=22) if both albumin adjusted s-calcium and plasma parathyroid hormone (p-iPTH) were above normal in absence of renal failure and vitamin-D insufficiency. To evaluate impact of minor calcium disturbance, suggesting normocalcemic HPT, the total cohort were divided into subjects with inappropriately elevated iPTH (IEP-group), based on above median value of both s-calcium (2.34mmol/L) and iPTH (4.24 pmol/L) ( n=387 minus the 22 with PHPT, in total 365) and subjects with normal calcium homeostasis (controls, n=1848). Group comparisons were made between PHPT-group and controls and IEP-group and controls. Results: The IEP-group performed inferior in all but one of the muscular functioning tests (all p <0.01, respectively) and the PHPT-group performed inferior in the time stand test (p<0.05). There were no significant group differences in fall or fracture prevalence. Conclusion: Elderly men with calcium disturbance, suggesting normocalcemic PHPT, had inferior physical performance than men with normal calcium homeostasis but it was not associated with higher fall or fracture prevalence.
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| 6. |
- Wu, Ping-Hsun, 1982-, et al.
(författare)
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The effect of fibroblast growth factor 23, vitamin D, and renal function on all-cause and cardiovascular mortality : The MrOS Sweden Study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), estimated glomerular filtration rate (eGFR), and vitamin D have been linked to mortality and cardiovascular disease, but the limited data addressed the combined effect of these factors on mortality. We investigated these different aspects of mineral bone disease biomarkers that portray independent and prognostic information in the Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort.Methods: The baseline level of FGF23, PTH, vitamin D, and eGFR was categorized as a normal and abnormal group. The mortality risk of mineral bone markers was analyzed by Kaplan-Meier curve for group difference evaluation and restricted cubic regression spline curve for continuous values of markers. We compare the importance of markers by random forest. Cox proportional regression models were used to evaluate the mortality risk of abnormal mineral bone markers components and their independent effect.Results: The MrOS cohort included 2706 men whose mean aged 75.4±3.18 years, 9.4% had diabetes, and 36.3% had hypertension. During a mean follow-up of 4.48 years, 383 all-cause deaths and 144 cardiovascular deaths were recorded. A high intact FGF23 level, low eGFR, and vitamin D deficiency were associated with increased all-cause mortality. Participants with a combination of high FGF23 level, low eGFR, and vitamin D deficiency had a twofold increased all-cause and cardiovascular mortality risk compared to those without abnormalities after adjusting for confounders. FGF23 was the most important factor related to all-cause mortality in random forest analysis, but the association was attenuated after controlling eGFR in the Cox model. In contrast, a low vitamin D remained to predict all-cause mortality independently.Conclusions: A higher FGF23, lower renal function, and lower vitamin D level are associated with increased all-cause and cardiovascular mortality in elderly men. Renal dysfunction influenced the mortality prediction of FGF23 but not vitamin D.
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