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- Pedersen, Nancy L., et al.
(författare)
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IGEMS : The Consortium on Interplay of Genes and Environment Across Multiple Studies - An Update
- 2019
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 22:6, s. 809-816
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Tidskriftsartikel (refereegranskat)abstract
- The Interplay of Genes and Environment across Multiple Studies (IGEMS) is a consortium of 18 twin studies from 5 different countries (Sweden, Denmark, Finland, United States, and Australia) established to explore the nature of gene-environment (GE) interplay in functioning across the adult lifespan. Fifteen of the studies are longitudinal, with follow-up as long as 59 years after baseline. The combined data from over 76,000 participants aged 14-103 at intake (including over 10,000 monozygotic and over 17,000 dizygotic twin pairs) support two primary research emphases: (1) investigation of models of GE interplay of early life adversity, and social factors at micro and macro environmental levels and with diverse outcomes, including mortality, physical functioning and psychological functioning; and (2) improved understanding of risk and protective factors for dementia by incorporating unmeasured and measured genetic factors with a wide range of exposures measured in young adulthood, midlife and later life.
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| 4. |
- Reynolds, Chandra A, et al.
(författare)
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A survey of ABCA1 sequence variation confirms association with dementia.
- 2009
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 30:9, s. 1348-54
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Tidskriftsartikel (refereegranskat)abstract
- We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1,567 Swedish dementia cases (including 1,275 with Alzheimer disease) and 2,203 controls, providing evidence of association with maximum significance at marker rs2230805 (odds ratio [OR]=1.39; 95% confidence interval [CI] 1.23-1.57, p=7.7x10(-8)). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of beta-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease.
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| 5. |
- Reynolds, Chandra A, et al.
(författare)
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Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.
- 2010
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 19:10, s. 2068-2078
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Tidskriftsartikel (refereegranskat)abstract
- We conducted dense linkage disequilibrium mapping of a series of 25 genes putatively involved in lipid metabolism in 1567 dementia cases (including 1270 with Alzheimer disease) and 2203 Swedish controls. Across a total of 448 tested genetic markers, the strongest evidence of association was as anticipated for APOE (rs429358 at p approximately 10(-72)) followed by a previously reported association of ABCA1 (rs2230805 at p approximately 10(-8)). In the present study we report two additional markers near the SREBF1 locus on chromosome 17p that were also significant after multiple testing correction (best p=3.1 x 10(-6) for marker rs3183702). There was no convincing evidence of association for remaining genes, including candidates highlighted from recent genome-wide association studies of plasma lipids (CELSR2/PSRC1/SORT1, MLXIPL, PCSK9, GALNT2, and GCKR). The associated markers near SREBF1 reside in a large linkage disequilibrium block, extending more than 400kb across 7 candidate genes. Secondary analyses of gene expression levels of candidates spanning the LD region together with an investigation of gene network context highlighted two possible susceptibility genes including ATPAF2 and TOM1L2. Several markers in strong LD (r(2)>0.7) with rs3183702 were found to be significantly associated with AD risk in recent genome-wide association studies with similar effect sizes, providing independent support of the current findings.
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| 6. |
- Reynolds, Chandra A, et al.
(författare)
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Sequence variation in SORL1 and dementia risk in Swedes.
- 2010
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6753 .- 1364-6745. ; 11:1, s. 139-42
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Tidskriftsartikel (refereegranskat)abstract
- The gene encoding the neuronal sortilin-related receptor SORL1 has been claimed to be associated with Alzheimer's disease (AD) by independent groups and across various human populations. We evaluated six genetic markers in SORL1 in a sample of 1,558 Swedish dementia cases (including 1,270 AD cases) and 2,179 controls. For both single-marker-based and haplotype-based analyses, we found no strong support for SORL1 as a dementia or AD risk-modifying gene in our sample in isolation nor did we observe association with AD/dementia-related traits, including cerebrospinal fluid beta-amyloid(1-42), tau levels, or age at onset. However, meta-analyses of markers in this study together with previously published studies on SORL1 encompassing in excess of 13,000 individuals does suggest significant association with AD (best odds ratio = 1.097; 95% confidence interval = 1.038-1.158, p = 0.001). All six markers were significant in meta-analyses and it is notable that they occur in two distinct linkage disequilibrium blocks. These data are consistent with either allelic heterogeneity or the existence of as yet untested functional variants and these will be important considerations in further attempts to evaluate the importance of sequence variation in SORL1 with AD risk.
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| 7. |
- Reynolds, Chandra A., et al.
(författare)
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Serum Lipid Levels and Cognitive Change in Late Life
- 2010
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 58:3, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess the effect of lipids and lipoproteins on longitudinal cognitive performance and cognitive health in late life and to consider moderating factors such as age and sex that may clarify conflicting prior evidence.DESIGN: Prospective cohort study.SETTING: A 16-year longitudinal study of health and cognitive aging.PARTICIPANTS: Eight hundred nineteen adults from the Swedish Adoption Twin Study of Aging aged 50 and older at first cognitive testing, including 21 twin pairs discordant for dementia.MEASUREMENTS: Up to five occasions of cognitive measurements encompassing verbal, spatial, memory, and perceptual speed domains across a 16-year span; baseline serum lipids and lipoproteins including high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo)A1, apoB, total serum cholesterol, and triglycerides.RESULTS: The effect of lipids on cognitive change was most evident before age 65. In women, higher HDL-C and lower apoB and triglycerides predicted better maintenance of cognitive abilities, particularly verbal ability and perceptual speed, than age. Lipid values were less predictive of cognitive trajectories in men and, where observed, were in the contrary direction (i.e., higher total cholesterol and apoB values predicted better perceptual speed performance though faster rates of decline). In twin pairs discordant for dementia, higher total cholesterol and apoB levels were observed in the twin who subsequently developed dementia.CONCLUSION: High lipid levels may constitute a more important risk factor for cognitive health before age 65 than after. Findings for women are consistent with clinical recommendations, whereas for men, the findings correspond with earlier age-associated shifts in lipid profiles and the importance of lipid homeostasis to cognitive health.
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| 8. |
- Bannon, Brittany L., et al.
(författare)
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Confirmatory factor analysis of illness behavior in the Swedish Adoption/Twin Study of Aging (SATSA)
- 2017
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Ingår i: Annals of Behavioral Medicine. - : Springer. - 0883-6612 .- 1532-4796. ; 51:Suppl. 1, s. S2654-S2655
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Tidskriftsartikel (refereegranskat)abstract
- Background: Illness behaviors—or affective, cognitive, and behavioral responses to symptoms of illness—predict patient outcomes, including symptom exacerbation and functional recovery, and they account for a large proportion of U.S. healthcare costs. Although priorcross-sectional work has examined illness behaviors like symptom reporting in isolation, the measurement of illness behavior using a longitudinal, multi-indicator approach has yet to be explored.Aim: We evaluated illness behavior as a latent, developmental construct in the Swedish Adoption/Twin Study of Aging (SATSA).Method: Participants were up to 1,886 individuals (from 1,223 twin pairs) ages 29 to 102 years (Mage baseline = 62.32 years; SD =13.69; 59% Female). Illness behavior indicators included somatic complaints, non-prescription medication use, pain-related disability and perceived illness complications. The psychomotor retardation subscale of the CES-D was used to index somatic complaints, and medication use was a simple composite of 9 dichotomous items on participants’ use of non-prescription medications, such as over-the-counter analgesics, in the previous month. Pain-related disability included a simple composite of three dichotomous items on the presence of neck,back, or shoulder pain that prevented participants from performing daily tasks or activities. Perceived illness disability was a composite of difference scores, calculated from subtracting a physician panel’s objective ratings of disability for each of 35 medical conditions (on a 3-pointscale; 1= Little or no disability; 3= Severe disability) from participants’ self-ratings of how much each of the same endorsed medical conditions interfered with their daily lives (on the same 3-point scale; 1= Not at all; 3= A lot). Positive composite scores reflected higher perceived disability relative to what was expected from the objective ratings, whereas a composite score of zero reflected “accuracy” or agreement in perceived illness complications. Confirmatory Factor Analysis (CFA) was used to evaluate invariance in the loadings of these four indicatorson a latent illness behavior factor across four questionnaire waves (1987-2004).Findings: Confirmatory factor analyses revealed moderate factor loadings of the four indicators (standardized loadings ranged from .49 to .52, all ps < .0001). Also, practical fit indices from the nested model comparisons suggested strong factorial invariance in the loadings across time (CFI = .96; TLI = .95, RMSEA= .03, 90% CI: [.026, .035]).Conclusion: Illness behavior as a latent, multi-indicator construct represents a promising focus for longitudinal work on behavior change and maintenance.
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| 10. |
- Dahl, Anna, 1975-, et al.
(författare)
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Accuracy of Recalled Body Weight-A Study with 20-years of Follow-Up
- 2013
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Ingår i: Obesity. - : John Wiley & Sons. - 1930-7381 .- 1930-739X. ; 21:6, s. 1293-1298
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Tidskriftsartikel (refereegranskat)abstract
- Objective:Weight changes may bean important indicator of an ongoing pathological process.Retrospective self-report might be the only possibility to capture prior weight. The objective of the study was to evaluate the accuracy of retrospective recallof body weight in old age and factors that might predict accuracy.Design and Methods:In 2007, 646 participants (mean age, 71.6 years) of the Swedish Adoption/Twin Study of Aging (SATSA)answered questions about their present weight and how much they weighed 20-years ago. Of these, 436 had self-reported their weighttwenty years earlier and among these 134 had also had their weight assessed at this time point.Results:Twenty yearretrospectively recalled weight underestimated the prior assessed weight by -1.89 ± 5.9 kg and underestimatedprior self-reported weight by -0.55 ±5.2 kg.Moreover, 82.4% of the sample were accurate within 10%, and 45.8% were accurate within 5% of their prior assessed weights;similarly, 84.2% and 58.0 %were accurate within 10% and 5% respectively, forprior self-reported weight. Current higher body mass index and preferences of reporting weights ending with zero or five was associated with an underestimation of prior weight, while greater weight change over 20 year, and low Mini-Mental State Scores (MMSE) (<25) led to an overestimation of prior weight.Conclusions:Recalled weight comes close to the assessed population mean, but at the individual level there is a large variation. The accuracy is affected by current BMI, changes in weight, end-digit preferences, and current cognitive ability. Recalled weight should be used with caution.
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