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- Maddock, Jane, et al.
(författare)
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Vitamin D and cognitive function : A Mendelian randomisation study.
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.
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- Sennerby, Ulf, et al.
(författare)
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Cardiovascular diseases and risk of hip fracture
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:15, s. 1666-1673
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Recent studies indicate common etiologies for cardiovascular disease (CVD) and osteoporotic fractures. OBJECTIVES: To examine the relation between CVD and risk of hip fracture in twins and evaluate the relative importance of genetics and lifestyle factors in this association. DESIGN, SETTING, AND PARTICIPANTS: A cohort of all 31,936 Swedish twins born from 1914-1944 was followed up from the age of 50 years. The National Patient Registry identified twins with CVDs and fractures from 1964 through 2005. Time-dependent exposures using Cox proportional hazard regression models were evaluated. MAIN OUTCOME MEASURE: Time to hip fracture after diagnosis of CVD. RESULTS: The crude absolute rate of hip fractures was 12.6 per 1000 person-years after a diagnosis of heart failure, 12.6 per 1000 person-years after a stroke, 6.6 per 1000 person-years after a diagnosis of peripheral atherosclerosis, and 5.2 per 1000 person-years after a diagnosis of ischemic heart disease compared with 1.2 per 1000 person-years for those without a CVD diagnosis. The multivariable-adjusted hazard ratio (HR) of hip fracture after a diagnosis of heart failure was 4.40 (95% confidence interval [CI], 3.43-5.63); after a stroke, the HR was 5.09 (95% CI, 4.18-6.20); after a diagnosis of peripheral atherosclerosis, the HR was 3.20 (95% CI, 2.28-4.50); and after an ischemic heart disease event, the HR was 2.32 (95% CI, 1.91-2.84). Identical twins without heart failure and stroke also had, after their co-twins had been exposed to these respective diseases, an increased rate of hip fracture. These sibling twins pseudoexposed for heart failure had a multivariable-adjusted HR of 3.74 (95% CI, 1.97-7.10) for hip fracture, whereas pseudoexposure for stroke had an HR of 2.29 (95% CI, 1.20-4.35). CONCLUSIONS: A diagnosis of CVD was significantly associated with risk of subsequent hip fracture. Increased risks in co-twins without an index diagnosis suggest genetic factors in the association between CVD and osteoporotic fractures.
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- Snellman, Greta, et al.
(författare)
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Seasonal genetic influence on serum 25-hydroxyvitamin D levels : a twin study
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:11, s. e7747-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although environmental factors, mainly nutrition and UV-B radiation, have been considered major determinants of vitamin D status, they have only explained a modest proportion of the variation in serum 25-hydroxyvitamin D. We aimed to study the seasonal impact of genetic factors on serum 25-hydroxyvitamin D concentrations. METHODOLOGY/PRINCIPAL FINDINGS: 204 same-sex twins, aged 39-85 years and living at northern latitude 60 degrees, were recruited from the Swedish Twin Registry. Serum 25-hydroxyvitamin D was analysed by high-pressure liquid chromatography and mass spectrometry. Genetic modelling techniques estimated the relative contributions of genetic, shared and individual-specific environmental factors to the variation in serum vitamin D. The average serum 25-hydroxyvitamin D concentration was 84.8 nmol/l (95% CI 81.0-88.6) but the seasonal variation was substantial, with 24.2 nmol/l (95% CI 16.3-32.2) lower values during the winter as compared to the summer season. Half of the variability in 25-hydroxyvitamin D during the summer season was attributed to genetic factors. In contrast, the winter season variation was largely attributable to shared environmental influences (72%; 95% CI 48-86%), i.e., solar altitude. Individual-specific environmental influences were found to explain one fourth of the variation in serum 25-hydroxyvitamin D independent of season. CONCLUSIONS/SIGNIFICANCE: There exists a moderate genetic impact on serum vitamin D status during the summer season, probably through the skin synthesis of vitamin D. Further studies are warranted to identify the genes impacting on vitamin D status.
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- Van Schijndel, Jessica E., et al.
(författare)
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Dual association of a TRKA polymorphism with schizophrenia
- 2011
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Ingår i: Psychiatric Genetics. - : Lippincott Williams & Wilkins. - 0955-8829 .- 1473-5873. ; 21:3, s. 125-131
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: An interaction between predisposing genes and environmental stressors is thought to underlie the neurodevelopmental disorder schizophrenia. In a targeted gene screening, we previously found that the minor allele of the single nucleotide polymorphism (SNP) rs6336 in the neurotrophic tyrosine kinase receptor 1 (NTRK1/TRKA) gene is associated with schizophrenia as a risk factor.METHODS: We genotyped the TRKA SNP in a total of eight independent Caucasian schizophrenia case-control groups.RESULT: Remarkably, although in five of the groups a higher frequency of the risk allele was indeed found in the patients compared with the controls, in the three other groups the SNP acted as a protective factor.CONCLUSION: An intriguing possibility is that this dual character of the TRKA SNP is caused by its interaction with endophenotypic and/or epistatic factors.
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- Wagner, Helene, et al.
(författare)
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Simply ask them about their balance-future fracture risk in a nationwide cohort study of twins
- 2009
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 169:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- The principal causal components of an osteoporotic fracture are a fall and weakened bone strength. While bone quality measures have been frequently studied, the ability of simple measures of impaired balance to predict fracture risk has received less attention. Computer-assisted telephone interviews were conducted between 1998 and 2000 among 24,598 Swedish twins aged 55 years or older. Impaired balance at the time of interview was reported by 2,890 (12%) of the twins. Twin pairs who were discordant with regard to impaired balance were selected for analysis and followed for fractures through 2005. In a pairwise analysis, the odds ratio for hip fracture was 3.13 (95% confidence interval (CI): 1.62, 6.05) among twins with impaired balance as compared with their co-twins with normal balance. When previously recognized clinical risk factors for osteoporotic fracture were considered in the model, the odds ratio for hip fracture with impaired balance was 3.88 (95% CI: 1.40, 10.72). Approximately 40% of all hip fractures were attributable to impaired balance. The odds ratios for any fracture and any osteoporotic fracture for twins with impaired balance were 2.00 (95% CI: 1.29, 3.11) and 2.39 (95% CI: 1.49, 3.82), respectively. These results imply that self-reported impaired balance is a novel and readily assessed risk factor for future fractures in the elderly.
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