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| 2. |
- Bakaysa, S.L., et al.
(författare)
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Telomere length predicts survival independent of genetic influences
- 2007
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Ingår i: Aging Cell. ; 63:6, s. 769-774
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres prevent the loss of coding genetic material during chromosomal replication. Previous research suggests that shorter telomere length may be associated with lower survival. Because genetic factors are important for individual differences in both telomere length and mortality, this association could reflect genetic or environmental pleiotropy rather than a direct biological effect of telomeres. We demonstrate through within-pair analyses of Swedish twins that telomere length at advanced age is a biomarker that predicts survival beyond the impact of early familial environment and genetic factors in common with telomere length and mortality. Twins with the shortest telomeres had a three times greater risk of death during the follow-up period than their co-twins with the longest telomere measurements [hazard ratio (RR) = 2.8, 95% confidence interval 1.1-7.3, P = 0.03].
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| 3. |
- Boesgaard, T. W., et al.
(författare)
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Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients--EUGENE2 study
- 2009
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Ingår i: PLoS One. - 1932-6203. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKROUND: A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. METHODOLOGY/RESULTS: Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2(nd) phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. CONCLUSION: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
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| 4. |
- Gatz, M, et al.
(författare)
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Accounting for the relationship between low education and dementia: a twin study.
- 2007
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Ingår i: Physiol Behav. ; , s. 232-237
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether the association between low education and greater risk of dementia is explained by genetic influences, using three different types of analyses. The HARMONY study (Swedish for "health" (Hälsa), "genes" (ARv), "environment" (Miljö), "and" (Och), and "new" (NY)) includes members of the Swedish Twin Registry who were aged 65 and older and alive in 1998, and who were screened and clinically assessed for dementia. There were 394 cases with dementia and 7786 unrelated controls. Analyses included co-twin control, tests for association between education and a measured genotype, and bivariate twin modeling. Low education was a significant risk factor for dementia both in case-control analyses (odds ratio=1.77, 95% confidence interval 1.38 to 2.28) and co-twin control analyses with monozygotic twin pairs (odds ratio=3.17, 95% confidence interval 1.26 to 7.93). Apolipoprotein E genotype was not associated with education and did not account for the relationship between education and dementia. Bivariate twin modeling showed that the association between education and dementia was not mediated by genetic influences in common between education and dementia. The association was mediated by shared environmental influences that were related to both dementia and to education. Low education is confirmed as a risk factor for dementia. Findings from three different analytic approaches showed that genetic influences did not explain this association.
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| 5. |
- Harel, O, et al.
(författare)
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Population inference with mortality and attrition in longitudinal studies on aging: a two-stage multiple imputation method.
- 2007
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Ingår i: Exp Aging Res. ; 33:2, s. 187-203
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge for inference regarding aging-related change in longitudinal studies is that of study attrition and population mortality. Inferences in longitudinal studies can account for attrition and mortality-related change as distinct processes, but this is made difficult when follow-up of all individuals (i.e., age at death) is not complete. This is a common problem because most longitudinal studies of aging either have incomplete follow-up or are still collecting data on subsequent outcomes, including time of death. A statistical approach is suggested for including time-to-death as a predictor in models with incomplete follow-up using a two-stage multiple-imputation procedure. An empirical example using data from the OCTO-Twin study is presented that shows the utility of his procedure for making inferences conditional on mortality when mortality data are incomplete
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| 6. |
- Johansson, Boo, et al.
(författare)
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Performance on Neurocognitive Tests by Co-twins to Dementia Cases Compared to Normal Control Twins
- 2005
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Ingår i: Journal of Geriatric Psychiatry and Neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 18:4, s. 202-207
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Tidskriftsartikel (refereegranskat)abstract
- Nondemented co-twins of twins who were diagnosed as demented were compared to randomly selected members of normal control twin pairs in which both mem-bers of the pair were nondemented. Nondemented co-twins included 23 monozy-gotic and 62 dizygotic twins; there were 27 normal control twins. Both monozy-gotic and dizygotic nondemented co-twins of dementia cases scored significantly lower than normal control twins on 5 of 10 cognitive tests. Moreover, monozygotic co-twins of dementia cases had a generally lower score profile than dizygotic co-twins of dementia cases did. These findings show that being at greater genetic risk for dementia is reflected in cognitive performance even in the absence of a diagnosis of dementia.
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| 7. |
- Xu, W., et al.
(författare)
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Mid- and late-life diabetes in relation to the risk of dementia: a population-based twin study.
- 2009
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:1, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to verify the association between diabetes and the risk of dementia, Alzheimer's disease, and vascular dementia in twins and to explore whether genetic and early-life environmental factors could contribute to this association. RESEARCH DESIGN AND METHODS: This study included 13,693 twin individuals aged > or =65 years. Dementia was diagnosed according to DSM-IV (Diagnostic Manual of Mental Disorders, 4th ed.) criteria. Information on diabetes was collected from the inpatient registry and self- or informant-reported history of diabetes. Data were analyzed following two strategies: 1) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models and 2) cotwin matched case-control analysis for dementia-discordant twin pairs using conditional logistic regression. RESULTS: Of all participants, 467 were diagnosed with dementia, including 292 with Alzheimer's disease and 105 with vascular dementia, and an additional 170 were diagnosed with questionable dementia. Diabetes was present in 1,396 subjects. In GEE models, diabetes was associated with adjusted odds ratios (ORs) (95% CI) of 1.89 (1.51-2.38) for dementia, 1.69 (1.16-2.36) for Alzheimer's disease, and 2.17 (1.36-3.47) for vascular dementia. Compared with late-life diabetes (onset age > or =65 years), the risk effect of mid-life diabetes (onset age <65 years) on dementia was stronger. Conditional logistic analysis of 210 dementia-discordant twin pairs led to ORs of 2.41 (1.05-5.51) and 0.68 (0.30-1.53) for dementia related to mid- and late-life diabetes, respectively. CONCLUSIONS: Diabetes increases the risk of Alzheimer disease and vascular dementia. The risk is stronger when diabetes occurs at mid-life than in late life. Genetic and early-life environmental factors might contribute to the late-life diabetes-dementia association but could not account for the mid-life diabetes-dementia association.
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| 8. |
- Iliadou, A., et al.
(författare)
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Risk of urinary incontinence symptoms in oral contraceptive users: a national cohort study from the Swedish Twin Register
- 2009
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Ingår i: Fertil Steril. ; 92:2, s. 428-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the impact of oral contraceptives on lower urinary tract dysfunction in premenopausal women. DESIGN: Nationwide cohort study. SETTING: National registry. PATIENT(S): A total of 10,791 women (born 1959-1985) from the population- based Swedish Twin Registry who participated in a web-based survey of common diseases. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Symptoms of urinary incontinence. RESULT(S): For users of oral contraception there was a significantly reduced risk for symptoms of stress urinary incontinence, mixed urinary incontinence, and urgency urinary incontinence. The reduction remained significant when adjusting for age, body mass index, and pregnancy history. A reduced prevalence of symptoms of overactive bladder in oral contraceptive users was also observed although the association was nonsignificant. There were no significant associations between lower urinary tract symptoms and women using a levonorgestrel-releasing intrauterine device compared with noncontraceptive users, with the exception of nocturia. CONCLUSION(S): Oral contraceptive use reduces the overall risk for symptoms of urinary incontinence.
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| 9. |
- Johansson, Boo, et al.
(författare)
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Cognitive abilities in late life, proximity to death and distance from birth
- 2006
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Ingår i: Cognitive abilities in late life, proximity to death and distance from birth. Paper presented at the 18th Nordic Congress in Gerontology, Jyväskylä, Finland..
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Konferensbidrag (refereegranskat)abstract
- Intra-individual change and continuity in cognitive abilities were examined as a conditional function of distance from birth (chronological age) and death in two Swedish population-based samples drawn from the H70 (70+; age-homogenous design) and the OCTO Twin (80+; age-heterogeneous design) studies. Examined cognitive domains included mental speed, memory, fluid, and crystallized abilities Three alternative time-based modelling approaches were used to fit the data a) an age-related approach b) a time-to–death-related approach, and c) a dual time structure component ap-proach including both age- and death-related time components. The death-related time structure accounts better for the data and age-related changes were largely attenuated when accounting for death-related changes, but death-related changes were relatively unaffected by the age-related sources of variance. The results emphasize that the reliance on age as a basic time structure in cognitive aging re-search can be doubtful and the importance of identifying diseases, co-morbidity and other health-related factors that account for cognitive decline in later life. Future studies need to identify and evaluate more specifically the time-related processes that increase the likelihood of death and produce decline in brain and cognitive functioning in later life.
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| 10. |
- Johansson, Boo, et al.
(författare)
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Complexity of work and risk of Alzheimer's disease: a population-based study of Swedish twins.
- 2005
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Ingår i: J Gerontology: Psychological Science. ; , s. 251-8
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association between risk of dementia or Alzheimer's disease (AD) and occupation by using measures of complexity of work with data, people, and things. The study included 10,079 members of the population-based Swedish Twin Registry who were participants in the HARMONY study. We diagnosed dementia by means of a two-stage procedure--cognitive impairment screening fol-lowed by full clinical evaluation. We analyzed data with case-control and cotwin control designs. The cotwin control design provides control over genetic and fa-milial factors. In the case-control study, controlling for age, gender, and level of education, we found that more complex work with people was associated with re-duced risk of AD. Greater complexity of work with people and data was protective in twin pairs discordant for AD. Findings suggest that greater complexity of work, and particularly complex work with people, may reduce the risk of AD.
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