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1.
Environ Health Perspect ; 127(10): 107012, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663781

RESUMO

BACKGROUND: Long-term exposure to particulate matter (PM) in ambient air has been associated with cardiovascular mortality, but few studies have considered incident disease in relation to PM from different sources. OBJECTIVES: We aimed to study associations between long-term exposure to different types of PM and sources, and incident ischemic heart disease (IHD) and stroke in three Swedish cities. METHODS: Based on detailed emission databases, monitoring data, and high-resolution dispersion models, we calculated source contributions to PM with aerodynamic diameter ≤10µm (PM10), PM with aerodynamic diameter ≤2.5µm (PM2.5), and black carbon (BC) from road wear, traffic exhaust, residential heating, and other sources in Gothenburg, Stockholm, and Umeå. Registry data for participants from four cohorts were used to obtain incidence of IHD and stroke for first hospitalization or death. We constructed time windows of exposure for same-year, 1- to 5-y, and 6- to 10-y averages preceding incidence from annual averages at residential addresses. Risk estimates were based on random effects meta-analyses of cohort-specific Cox proportional hazard models. RESULTS: We observed 5,166 and 3,119 incident IHD and stroke cases, respectively, in 114,758 participants. Overall, few consistent associations were observed between the different air pollution measures and IHD or stroke incidence. However, same-year levels of ambient locally emitted BC (range: 0.01-4.6 µg/m3) were associated with a 4.0% higher risk of incident stroke per interquartile range (IQR), 0.30 µg/m3 [95% confidence interval (CI): 0.04, 7.8]. This association was primarily related to BC from traffic exhaust. PM10 (range: 4.4-52 µg/m3) and PM2.5 (range: 2.9-22 µg/m3) were not associated with stroke. Associations with incident IHD were observed only for PM2.5 exposure from residential heating. DISCUSSION: Few consistent associations were observed between different particulate components and IHD or stroke. However, long-term residential exposure to locally emitted BC from traffic exhaust was associated with stroke incidence. The comparatively low exposure levels may have contributed to the paucity of associations. https://doi.org/10.1289/EHP4757.

2.
Biol Psychiatry ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

3.
Clin Epigenetics ; 11(1): 130, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477183

RESUMO

BACKGROUND: Alzheimer's disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized that the disease-associated DNA methylation signatures are detectable in the peripheral blood of discordant twin pairs. RESULTS: Comparison of 23 disease discordant Finnish twin pairs with reduced representation bisulfite sequencing revealed peripheral blood DNA methylation differences in 11 genomic regions with at least 15.0% median methylation difference and FDR adjusted p value ≤ 0.05. Several of the affected genes are primarily associated with neuronal functions and pathologies and do not display disease-associated differences in gene expression in blood. The DNA methylation mark in ADARB2 gene was found to be differentially methylated also in the anterior hippocampus, including entorhinal cortex, of non-twin cases and controls. Targeted bisulfite pyrosequencing of the DNA methylation mark in ADARB2 gene in 62 Finnish and Swedish twin pairs revealed that, in addition to the disease status, DNA methylation of this region is influenced by gender, age, zygosity, APOE genotype, and smoking. Further analysis of 120 Swedish twin pairs indicated that this specific DNA methylation mark is not predictive for Alzheimer's disease and becomes differentially methylated after disease onset. CONCLUSIONS: DNA methylation differences can be detected in the peripheral blood of twin pairs discordant for Alzheimer's disease. These DNA methylation signatures may have value as disease markers and provide insights into the molecular mechanisms of pathogenesis. We found no evidence that the DNA methylation marks would be associated with gene expression in blood. Further studies are needed to elucidate the potential importance of the associated genes in neuronal functions and to validate the prognostic or diagnostic value of the individual marks or marker panels.

4.
J Am Geriatr Soc ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529624

RESUMO

OBJECTIVE: To determine whether there is an association between osteoarthritis (OA) and incident social isolation using data from the European Project on OSteoArthritis (EPOSA) study. DESIGN: Prospective, observational study with 12 to 18 months of follow-up. SETTING: Community dwelling. PARTICIPANTS: Older people living in six European countries. MEASUREMENTS: Social isolation was assessed using the Lubben Social Network Scale and the Maastricht Social Participation Profile. Clinical OA of the hip, knee, and hand was assessed according to American College of Rheumatology criteria. Demographic characteristics, including age, sex, multijoint pain, and medical comorbidities, were assessed. RESULTS: Of the 1967 individuals with complete baseline and follow-up data, 382 (19%) were socially isolated and 1585 were nonsocially isolated at baseline; of these individuals, 222 (13.9%) experienced social isolation during follow-up. Using logistic regression analyses, after adjustment for age, sex, and country, four factors were significantly associated with incident social isolation: clinical OA, cognitive impairment, depression, and worse walking time. Compared to those without OA at any site or with only hand OA, clinical OA of the hip and/or knee, combined or not with hand OA, led to a 1.47 times increased risk of social isolation (95% confidence interval = 1.03-2.09). CONCLUSION: Clinical OA, present in one or two sites of the hip and knee, or in two or three sites of the hip, knee, and hand, increased the risk of social isolation, adjusting for cognitive impairment and depression and worse walking times. Clinicians should be aware that individuals with OA may be at greater risk of social isolation.

5.
Hum Mol Genet ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518406

RESUMO

Humans are social animals that experience intense suffering when they perceive a lack of social connection. Modern societies are experiencing an epidemic of loneliness. While the experience of loneliness is universally human, some people report experiencing greater loneliness than others. Loneliness is more strongly associated with mortality than obesity, emphasizing the need to understand the nature of the relationship between loneliness and health. While it is intuitive that circumstantial factors such as marital status and age influence loneliness, there is also compelling evidence of a genetic predisposition towards loneliness. To better understand the genetic architecture of loneliness and its relationship with associated outcomes, we extended the genome-wide association study (GWAS) meta-analysis of loneliness to 511 280 subjects, and detect 19 significant genetic variants from 16 loci, including four novel loci, as well as 58 significantly associated genes. We investigated the genetic overlap with a wide range of physical and mental health traits by computing genetic correlations and by building loneliness polygenic scores in an independent sample of 18 498 individuals with electronic health record data to conduct a PheWAS with. A genetic predisposition towards loneliness was associated with cardiovascular, psychiatric, and metabolic disorders, and triglycerides and high-density lipoproteins. Mendelian randomization analyses showed evidence of a causal, increasing, effect of both BMI and body fat on loneliness. Our results provide a framework for future studies of the genetic basis of loneliness and its relationship to mental and physical health.

6.
Twin Res Hum Genet ; : 1-8, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31544729

RESUMO

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.

7.
Psychosom Med ; 81(9): 799-807, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469771

RESUMO

OBJECTIVE: Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, that is, the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences. METHODS: Data were derived from the UK Biobank (UKB; n = 274,951), the Australian Over 50's Study (AO50; n = 2849), and the Swedish Twin Registry (Screening Across the Lifespan of Twins Study [SALT], n = 18,960; The Swedish Adoption/Twin Study of Aging [SATSA], n = 1365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50, and SATSA and longitudinally in SALT (25-29 years of follow-up) and SATSA (6 and 23 years of follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty. RESULTS: High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted ß [95% confidence intervals] in UKB = 0.32 [0.32-0.33]; AO50 = 0.35 [0.31-0.39]; SATSA = 0.33 [0.27-0.39]) and longitudinally up to 29 years (SALT = 0.24 [0.22-0.25]; SATSA 6 years = 0.31 [0.24-0.38]; SATSA 23 years = 0.16 [0.07-0.25]). When adjusting for underlying shared genetic and environmental factors, the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total ß = 0.059 [0.055-0.062]). CONCLUSIONS: Neuroticism in midlife predicts frailty in late life. Neuroticism may have a causal influence on frailty, whereas both environmental and genetic influences, including neuroticism-associated common genetic variants, contribute to this relationship.

8.
Int J Epidemiol ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363756

RESUMO

BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium. METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries. RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH. CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.

9.
EBioMedicine ; 45: 487-494, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31300347

RESUMO

BACKGROUND: High circulating low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerosis and age-associated cardiovascular events. Long-term dyslipidaemia could contribute to the development of frailty in older individuals through its role in determining cardiovascular health and potentially other physiological pathways. METHODS: We conducted Mendelian randomization (MR) analyses using genetic variants to estimate the effects of long-term LDL-C modification on frailty in UK Biobank (n = 378,161). Frailty was derived from health questionnaire and interview responses at baseline when participants were aged 40 to 69 years, and calculated using an accumulation-of-deficits approach, i.e. the frailty index (FI). Several aggregated instrumental variables (IVs) using 50 and 274 genetic variants were constructed from independent single-nucleotide polymorphisms (SNPs) to instrument circulating LDL-C concentrations. Specific sets of variants in or near genes that encode six lipid-lowering drug targets (HMGCR, PCSK9, NPC1L1, APOB, APOC3, and LDLR) were used to index effects of exposure to related drug classes on frailty. SNP-LDL-C effects were available from previously published studies. SNP-FI effects were obtained using adjusted linear regression models. Two-sample MR analyses were performed with the IVs as instruments using inverse-variance weighted, MR-Egger, weighted median, and weighted mode methods. To address the stability of the findings, MR analyses were also performed using i) a modified FI excluding the cardiometabolic deficit items and ii) data from comparatively older individuals (aged ≥60 years) only. Several sensitivity analyses were also conducted. FINDINGS: On average 0.14% to 0.23% and 0.16% to 0.31% decrements in frailty were observed per standard deviation reduction in LDL-C exposure, instrumented by the general IVs consisting of 50 and 274 variants, respectively. Consistent, though less precise, associations were observed in the HMGCR-, APOC3-, NPC1L1-, and LDLR-specific IV analyses. In contrast, results for PCSK9 were in the same direction but more modest, and null for APOB. All sensitivity analyses produced similar findings. INTERPRETATION: A genetically-predicted life-long lowering of LDL-C is associated with decreased frailty in midlife and older age, representing supportive evidence for LDL-C's role in multiple health- and age-related pathways. The use of lipid-lowering therapeutics with varying mechanisms of action may differ by the extent to which they provide overall health benefits.

10.
Am J Geriatr Psychiatry ; 27(11): 1177-1188, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31235427

RESUMO

OBJECTIVE: To test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia. METHODS: A prospective national matched cohort study from Israel (N = 71,515) without dementia (2002-2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes. RESULTS: In the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47. CONCLUSION: In this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.

11.
Diabetologia ; 62(8): 1403-1411, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31172222

RESUMO

AIMS/HYPOTHESIS: We aimed to examine the association between midlife type 2 diabetes mellitus and cerebrovascular disease (CBD) in late life, and further to explore whether genetic and early-life familial environmental factors (such as shared childhood socioeconomic status and adolescent environment) play a role in this association. METHODS: In this prospective nested case-control study based on the Swedish Twin Registry, 33,086 twin individuals who were born in 1958 or earlier and were CBD-free before the age of 60 were included. Midlife (40-59 years) type 2 diabetes was ascertained from self-report, the National Patient Registry (NPR) and glucose-lowering medication use. CBD diagnosis (cerebral infarction, occlusion of cerebral arteries, subarachnoid haemorrhage, intracerebral haemorrhage and unspecified CBD) and onset age were identified from the NPR. Late-life CBD was defined as CBD onset age ≥60 years. Generalised estimating equation (GEE) models were used to analyse unmatched case-control data (adjusted for the clustering of twins within a pair). Conditional logistic regression was used in co-twin matched case-control analyses in CBD-discordant twin pairs. RESULTS: Of all the participants, 1248 (3.8%) had midlife type 2 diabetes and 3121 (9.4%) had CBD in late life. In GEE models adjusted for age, sex, education, BMI, smoking, alcohol consumption, marital status, hypertension and heart disease, the ORs (95% CIs) of type 2 diabetes were 1.29 (1.03, 1.61) for cerebral infarction, 2.03 (1.20, 3.44) for occlusion of cerebral arteries, 0.52 (0.12, 2.21) for subarachnoid haemorrhage and 0.78 (0.45, 1.36) for intracerebral haemorrhage. In multi-adjusted conditional logistic regression, the OR of the type 2 diabetes-cerebral infarction association was 0.96 (0.51, 1.80). The differences in ORs from the GEE and co-twin control analyses were not statistically significant (p = 0.780). CONCLUSIONS/INTERPRETATION: Midlife type 2 diabetes is significantly associated with increased risk of cerebral infarction and occlusion of cerebral arteries, but not intracerebral haemorrhage or subarachnoid haemorrhage in late life. Genetic and early-life familial environmental factors do not appear to account for the type 2 diabetes-cerebral infarction association, but further clarification is needed.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31222213

RESUMO

BACKGROUND: The aim was to develop a functional aging index (FAI) that taps four body systems: sensory (vision and hearing), pulmonary, strength (grip strength), and movement/balance (gait speed) and to test the predictive value of FAI for entry into care and mortality. METHOD: Growth curve models and cox regression models were applied to data from 1695 individuals from three Swedish longitudinal studies of aging. Participants were aged 45 to 93 at intake and data from up to 8 follow-up waves were available. RESULTS: The rate of change in FAI was twice as fast after age 75 as before, women demonstrated higher mean FAI, but no sex differences in rates of change with chronological age were identified. FAI predicted entry into care and mortality, even when chronological age and a frailty index were included in the models. Hazard ratios indicated FAI was a more important predictor of entry into care for men than women; whereas it was a stronger predictor of mortality for men than women. CONCLUSIONS: Measures of biological aging and functional aging differ in their predictive value for entry into care and mortality for men and women, suggesting that both are necessary for a complete picture of the aging process across genders.

13.
BMC Med ; 17(1): 94, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31088449

RESUMO

BACKGROUND: Frailty index (FI) is a well-established predictor of all-cause mortality, but less is known for cause-specific mortality and whether familial effects influence the associations. Middle-aged individuals are also understudied for the association between FI and mortality. Furthermore, the population mortality impact of frailty remains understudied. METHODS: We estimated the predictive value of FI for all-cause and cause-specific mortality, taking into account familial factors, and tested whether the associations are time-dependent. We also assessed the proportion of all-cause and cause-specific deaths that are attributable to increased levels of frailty. We analyzed 42,953 participants from the Screening Across the Lifespan Twin Study (aged 41-95 years at baseline) with up to 20 years' mortality follow-up. The FI was constructed using 44 health-related items. Deaths due to cardiovascular disease (CVD), respiratory-related causes, and cancer were considered in the cause-specific analysis. Generalized survival models were used in the analysis. RESULTS: Increased FI was associated with higher risks of all-cause, CVD, and respiratory-related mortality, with the corresponding hazard ratios of 1.28 (1.24, 1.32), 1.31 (1.23, 1.40), and 1.23 (1.11, 1.38) associated with a 10% increase in FI in male single responders, and 1.21 (1.18, 1.25), 1.27 (1.15, 1.34), and 1.26 (1.15, 1.39) in female single responders. No significant associations were observed for cancer mortality. No attenuation of the mortality associations in unrelated individuals was observed when adjusting for familial effects in twin pairs. The associations were time-dependent with relatively greater effects observed in younger ages. Before the age of 80, the proportions of deaths attributable to FI levels > 0.21 were 18.4% of all-cause deaths, 25.4% of CVD deaths, and 20.4% of respiratory-related deaths in men and 19.2% of all-cause deaths, 27.8% of CVD deaths, and 28.5% of respiratory-related deaths in women. After the age of 80, the attributable proportions decreased, most notably for all-cause and CVD mortality. CONCLUSIONS: Increased FI predicts higher risks of all-cause, CVD, and respiratory-related mortality independent of familial effects. Increased FI presents a relatively greater risk factor at midlife than in old age. Increased FI has a significant population mortality impact that is greatest through midlife until the age of 80.

14.
BMC Musculoskelet Disord ; 20(1): 227, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101033

RESUMO

BACKGROUND: The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods. METHODS: The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis. RESULTS: Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function. CONCLUSIONS: The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.

15.
Int J Epidemiol ; 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30929008

RESUMO

BACKGROUND: Despite advances in life expectancy, low socioeconomic status is associated with a shorter lifespan. This study was conducted to investigate socioeconomic differences in mortality by comparing preventable with non-preventable causes of death in 39 506 participants from the Swedish Twin Registry born before 1935. METHODS: Childhood social class, own education, own social class and social mobility were used as separate indicators of socioeconomic status. These data were linked to the Swedish Cause of Death Register. Cause of death was categorized as preventable or non-preventable mortality according to indicators presented in the Avoidable Mortality in the European Union (AMIEHS) atlas. Using Cox proportional hazard models, we tested the association between the socioeconomic measures and all-cause mortality, preventable mortality and non-preventable mortality. Additional co-twin control analyses indicated whether the associations reflected genetic confounding. RESULTS: The social gradient for mortality was most prominent for the adult socioeconomic measures. There was a social gradient in both preventable mortality and non-preventable mortality, but with an indication of a moderately stronger effect in preventable causes of death. In analyses of social mobility, those who experienced life-time low socioeconomic status (SES) or downward social mobility had an increased mortality risk compared with those with life-time high SES and upward social mobility. Adjustments for genetic confounding did not change the observed associations for education, social class or social mobility and mortality. In the co-twin control analyses of reared-apart twins, the association between childhood social class and mortality weakened, indicating possible genetic influences on this association. CONCLUSIONS: Our results indicate that there is an association between low adult socioeconomic status and increased mortality independent of genetic endowment. Thus, we do not find support for indirect social selection as the basis for mortality inequalities in Sweden.

16.
Eur Respir J ; 53(5)2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30956207

RESUMO

Depression, anxiety and high neuroticism (affective traits) are often comorbid with asthma. A causal direction between the affective traits and asthma is difficult to determine; however, there may be a common underlying pathway attributable to shared genetic factors. Our aim was to determine whether a common genetic susceptibility exists for asthma and each of the affective traits.An adult cohort from the Swedish Twin Registry underwent questionnaire-based health assessments (n=23 693) and genotyping (n=15 908). Firstly, questionnaire-based associations between asthma and affective traits were explored. This was followed by genetic analyses: 1) polygenic risk scores (PRS) for affective traits were used as predictors of asthma in the cohort, and 2) genome-wide association results from UK Biobank were used in linkage-disequilibrium score regression (LDSC) to quantify genetic correlations between asthma and affective traits. Analyses found associations between questionnaire-based asthma and affective traits (OR 1.67, 95% CI 1.50-1.86 major depression; OR 1.45, 95% CI 1.30-1.61 anxiety; and OR 1.60, 95% CI 1.40-1.82 high neuroticism). Genetic susceptibility for neuroticism explained the variance in asthma with a dose-response effect; that is, study participants in the highest neuroticism PRS quartile were more likely to have asthma than those in the lowest quartile (OR 1.37, 95% CI 1.17-1.61). Genetic correlations were found between depression and asthma (rg=0.17), but not for anxiety or neuroticism.We conclude that the observed comorbidity between asthma and the affective traits may in part be due to shared genetic influences between asthma and depression (LDSC) and neuroticism (PRS), but not anxiety.

17.
Occup Environ Med ; 76(4): 201-207, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30804165

RESUMO

BACKGROUND: There is limited evidence from longitudinal studies on transportation noise from different sources and development of ischaemic heart disease (IHD) and stroke. OBJECTIVES: This cohort study assessed associations between exposure to noise from road traffic, railway or aircraft and incidence of IHD and stroke. METHODS: In a cohort of 20 012 individuals from Stockholm County, we estimated long-term residential exposure to road traffic, railway and aircraft noise. National Patient and Cause-of-Death Registers were used to identify IHD and stroke events. Information on risk factors was obtained from questionnaires and registers. Adjusted HR for cardiovascular outcomes related to source-specific noise exposure were computed using Cox proportional hazards regression. RESULTS: No clear or consistent associations were observed between transportation noise and incidence of IHD or stroke. However, noise exposure from road traffic and aircraft was related to IHD incidence in women, with HR of 1.11 (95% CI 1.00 to 1.22) and 1.25 (95% CI 1.09 to 1.44) per 10 dB Lden, respectively. For both sexes taken together, we observed a particularly high risk of IHD in those exposed to all three transportation noise sources at≥45 dB Lden, with a HR of 1.57 (95% CI 1.06 to 2.32), and a similar tendency for stroke (HR 1.42; 95% CI 0.87 to 2.32). CONCLUSION: No overall associations were observed between transportation noise exposure and incidence of IHD or stroke. However, there appeared to be an increased risk of IHD in women exposed to road traffic or aircraft noise as well as in those exposed to multiple sources of transportation noise.

18.
Alzheimers Dement ; 15(4): 534-542, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30777379

RESUMO

INTRODUCTION: We evaluated whether hospitalization with or without surgery increases risk for dementia or Alzheimer's disease. METHODS: A clinical sample (843 clinically diagnosed dementia cases; 1686 matched nondemented individuals) was identified from Swedish Twin Registry studies. A register-based sample (4293 cases; 21,465 matched controls) was identified by linkage of Swedish Twin Registry to Swedish Patient Registry records. Apolipoprotein E (APOE) status and within-pair comparisons of dementia discordant twins indicated genetic susceptibility. RESULTS: Nonsurgical hospitalization is associated with greater dementia risk than hospitalization with surgical intervention. In the register sample, thoracic, abdominal, and major orthopedic procedures entailed dementia risk; in the clinical sample, orthopedic alone. Within-pair analyses indicate that associations in part reflect genetic susceptibility in common to hospitalization and dementia. Potential gene-environment interactions were indicated by greater risk due to hospitalization among APOE ε4 noncarriers. DISCUSSION: We confirm hospitalization as a risk factor for dementia, with repeated hospitalizations a more important risk factor than surgery.

19.
EBioMedicine ; 40: 710-716, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30704927

RESUMO

BACKGROUND: Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood. METHODS: In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79 years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks. FINDINGS: A model incorporating additive genetic (A) and person-specific environmental (E) influences best explained the variation in both clocks. Heritability was estimated at 55% at baseline and at 51% at follow-up for the Horvath clock and 34% at baseline and 41% at follow-up for the Levine clock. For the Horvath clock, new sources of A influences emerged at follow-up, whereas for the Levine clock, the same A influences accounted for the genetic variance at both measurement occasions. The cross-time phenotypic correlations, 0·52 for the Horvath clock and 0·36 for the Levine clock, were mediated primarily by genetic factors, whereas the person-specific environmental factors were completely different at the two measurement occasions. INTERPRETATION: For both clocks, new sources of person-specific environmental influences emerge with age. The epigenetic clocks might thus be responsive to new environmental stimuli even at old age. FUND: NIH (R01;AG04563;AG10175;AG028555) the MacArthur Foundation Research Network on Successful Aging, FAS/FORTE (97:0147:1B;2009-0795), Swedish Research Council (825-2007-7460;825-2009-6141;521-2013-8689;2015-03255;2015-06796;2018-02077), FORTE (2013-2292), the Strategic Research Program in Epidemiology at KI, VELUX FOUNDATION, NIA (P01-AG08761), the EU (FP7/2007-2011;259679) and The Danish National Program for Research Infrastructure 2007 (9-063256).


Assuntos
Envelhecimento/genética , Meio Ambiente , Epigênese Genética , Interação Gene-Ambiente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Perfilação da Expressão Gênica , Humanos , Estudos Longitudinais , Masculino , Modelos Biológicos , Fenótipo , Característica Quantitativa Herdável , Suécia , Gêmeos
20.
Biogerontology ; 20(3): 321-329, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30666568

RESUMO

Recent research has shown that markers of biological age, such as leukocyte telomere length (LTL), epigenetic clocks and the frailty index (FI) are predictive of mortality and age-related diseases. However, whether these markers associate with the need for care in old age, thereby having utility in reflecting dependency, is unclear. This study was undertaken to analyze whether LTL, two epigenetic clocks-the DNA methylation age (DNAmAge) and DNAm PhenoAge-and the FI are associated with the need for regular care in up to 604 individuals (aged 48-94 years) participating in the Swedish Adoption/Twin Study of Aging. Need for regular care was defined as receiving formal or informal help in daily routines at least once per week. Logistic regression adjusted for age, sex and education was used in the analysis. The predictive accuracies, assessed as the area under the curve (AUC) for the significant biological age measures were further compared to the accuracies of the limitations in activities of daily living (ADL) and instrumental ADL (IADL). Neither LTL nor the epigenetic clocks were associated with the need for care, whereas the FI was; odds ratio for 10% increase in FI 3.54 (95% confidence interval 2.32-5.41). The FI also demonstrated higher predictive accuracy than the ADL score (FI AUC 0.80 vs. ADL score AUC 0.62; p < 0.001 for equality of the AUCs), whereas the difference between FI AUC (0.80) and IADL score AUC (0.75) was not significant (p = 0.238). The FI might thus be a useful marker for the need for care.

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