| 1. |
- Silventoinen, Karri, et al.
(author)
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Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
- 2020
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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| 2. |
- Li, Chen, et al.
(author)
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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- 2020
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In: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
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Journal article (peer-reviewed)abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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| 3. |
- van Zuydam, Natalie R., et al.
(author)
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Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
- 2020
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In: Circulation. - : Lippincott Williams & Wilkins. - 2574-8300. ; 13:6, s. 640-648
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Journal article (peer-reviewed)abstract
- BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
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| 4. |
- Byhamre, Marja Lisa, et al.
(author)
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Swedish snus use is associated with mortality : a pooled analysis of eight prospective studies
- 2020
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:6, s. 2041-2050
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Journal article (peer-reviewed)abstract
- BACKGROUND: The health consequences of the use of Swedish snus, including its relationship with mortality, have not been fully established. We investigated the relationship between snus use and all-cause and cause-specific mortality (death due to cardiovascular diseases, cancer diseases and all other reasons, respectively) in a nationwide collaborative pooling project.METHODS: We followed 169 103 never-smoking men from eight Swedish cohort studies, recruited in 1978-2010. Shared frailty models with random effects at the study level were used in order to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of mortality associated with snus use.RESULTS: Exclusive current snus users had an increased risk of all-cause mortality (aHR 1.28, 95% CI 1.20-1.35), cardiovascular mortality (aHR 1.27, 95% CI 1.15-1.41) and other cause mortality (aHR 1.37, 95% CI 1.24-1.52) compared with never-users of tobacco. The risk of cancer mortality was also increased (aHR 1.12, 95% CI 1.00-1.26). These mortality risks increased with duration of snus use, but not with weekly amount.CONCLUSIONS: Snus use among men is associated with increased all-cause mortality, cardiovascular mortality, with death from other causes and possibly with increased cancer mortality.
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| 5. |
- Dintica, Christina S., et al.
(author)
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The relation of poor mastication with cognition and dementia risk : a population-based longitudinal study
- 2020
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In: Aging. - : Impact Journals LLC. - 1945-4589. ; 12:9, s. 8536-8548
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Journal article (peer-reviewed)abstract
- We investigated the effect of poor masticatory ability on cognitive trajectories and dementia risk in older adults. 544 cognitively intact adults aged =50 were followed for up to 22 years. Cognitive domains (verbal, spatial/fluid, memory, and perceptual speed) were assessed at baseline and follow-ups. Dementia was ascertained according to standard criteria. Masticatory ability was assessed using the Eichner Index and categorized according to the number of posterior occlusal zones: A (all four), B (3-1), and C (none).At baseline, 147 (27.0%) participants were in Eichner category A, 169 (31.1%) in B and 228 (41.9%) in C. After the age of 65, participants in Eichner category B and C showed an accelerated decline in spatial/fluid abilities (beta: -0.16, 95% CI: -0.30 to -0.03) and (beta: -0.15, 95% CI: -0.28 to -0.02), respectively. Over the follow-up, 52 incident dementia cases were identified. Eichner categories B or C were not associated with an increased risk of dementia, compared to category A (Hazard Ratio [HR]: 0.83, 95% CI: 0.39 to 1.76 and HR: 0.63, 95% CI: 0.30 to 1.29, respectively).Poor masticatory ability is associated with an accelerated cognitive decline in fluid/spatial abilities, however it was not related to a higher risk of dementia.
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| 6. |
- Finkel, Deborah, et al.
(author)
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Longitudinal twin study of subjective health : Differences in genetic and environmental components of variance across age and sex
- 2020
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In: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press. - 1079-5014 .- 1758-5368. ; 75:1, s. 1-10
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Journal article (peer-reviewed)abstract
- Objective: The current analysis examines sex differences in longitudinal changes in genetic and environmental influences on three measures of subjective health.Method: Sample includes 7372 twins (mean intake age = 73.22) with up to 8 waves of measurement (mean = 3.1). Three subjective health (SH) items were included: general self-rated health (SRH), health compared to age peers (COMP), and impact of health on activities (ACT) which previous research shows capture different frames of reference.Results: Latent growth curve modeling indicated significant differences across gender and frame of reference in trajectories of change with age and in genetic and environmental contributions to change. Men have higher mean scores on all three SH measures, indicating better SH, but there were no sex differences in pattern of change with age. Accelerating declines with age were found for SRH and ACT, whereas COMP improved with age. Results indicated more genetic variance for women than men, but declining genetic variance for both after age 70. Increasing shared environmental variance with increasing age was also found for both sexes.Discussion: As aging triggers a re-evaluation of the meaning of "good health," physical aspects of health may become less important and shared cultural conceptions of health may become more relevant. This change in conceptions of good health may reflect both aging and the change in composition of the elderly population as a result of selective survival.
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| 7. |
- Finkel, Deborah, et al.
(author)
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Role of motor function and lung function in pathways to ageing and decline
- 2020
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In: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 32, s. 2479-2487
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Journal article (peer-reviewed)abstract
- BackgroundExtensive research has investigated the association between age changes in various domains, including lung function and motor function. However, a few analyses have tested models that incorporate bidirectional longitudinal influences between lung and motor function to test the temporal chain of events in the disability process. Dual change score models (DCSM) assist with identification of leading indicators of change by leveraging longitudinal data to examine the extent to which changes in one variable influence subsequent changes in a second variable, and vice versa.AimsThe purpose of the current-analysis study was to apply DCSM to data from the Swedish Adoption/Twin Study of ageing to examine the nature of the longitudinal relationship between motor functioning and lung function.MethodsThree motor functioning factors were created from 20 performance measures, including measures of balance, flexibility, and fine motor skills. Peak expiratory flow measured lung function. Participants were 829 adults aged 50–88 at the first of 9 waves of testing covering a 27-year follow-up period; 80% participated in at least three waves.ResultsModel comparisons indicated that decline in lung function preceded and contributed to subsequent decline in motor function.DiscussionCombined with previous results, these results suggest that declining lung function results in increasing difficulties in motor function, which contribute to subsequent declines in multiple domains.ConclusionUnderstanding the cascade of events that can lead to dependence can help in the development of interventions targeted early in the disablement process.
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| 8. |
- Hong, Mun-Gwan, et al.
(author)
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Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality
- 2020
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In: Life Science Alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:10, s. e202000817-
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Journal article (peer-reviewed)abstract
- Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50–92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 × 10−6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12–1.39; P = 6.45 × 10−5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7–9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.
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| 9. |
- Kang, Xiaoying, et al.
(author)
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Clostridium difficile infection and risk of Parkinson's disease : A Swedish population-based cohort study
- 2020
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In: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 27:11, s. 2134-2141
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Journal article (peer-reviewed)abstract
- BACKGROUND: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). This study examined whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD.METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥ 35 years were identified from the Swedish Population and Housing Census 1990 and followed during 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs outpatient), presence of recurrent infections, and pre-infection use of antibiotics.RESULTS: Amongst the study population (N = 4,670,423), 34,868 (0.75%) had a history of CDI. A total of 165 and 47,035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among CDI group (hazard ratio: 1.16, 95% confidence interval: 1.00-1.36), which was mainly driven by increased PD risk within the first 2 years since CDI diagnosis (hazard ratio: 1.38, 95% confidence interval: 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups.CONCLUSIONS: CDI may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.
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| 10. |
- Karlsson, Ida K., et al.
(author)
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Replicating associations between DNA methylation and body mass index in a longitudinal sample of older twins
- 2020
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In: International Journal of Obesity. - : Springer Nature. - 0307-0565 .- 1476-5497. ; 44:6, s. 1397-1405
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Journal article (peer-reviewed)abstract
- Background:There is an important interplay between epigenetic factors and body weight, and previous work has identified ten sites where DNA methylation is robustly associated with body mass index (BMI) cross-sectionally. However, interpretation of the associations is complicated by the substantial changes in BMI often occurring in late-life, and the fact that methylation is often driven by genetic variation. This study therefore investigated the longitudinal association between these ten sites and BMI from midlife to late-life, and whether associations persist after controlling for genetic factors.Methods:We used data from 535 individuals (mean age 68) in the Swedish Adoption/Twin Study of Aging (SATSA) with longitudinal measures of both DNA methylation from blood samples and BMI, spanning up to 20 years. Methylation levels were measured with the Infinium Human Methylation 450K or Infinium MethylationEpic array, with seven of the ten sites passing quality control. Latent growth curve models were applied to investigate longitudinal associations between methylation and BMI, and between–within models to study associations within twin pairs, thus adjusting for genetic factors.Results:Baseline DNA methylation levels at five of the seven sites were associated with BMI level at age 65 (cg00574958 [CPT1A]; cg11024682 [SREBF1]), and/or change (cg06192883 [MYO5C]; cg06946797 [RMI2]; cg08857797 [VPS25]). For four of the five sites, the associations remained comparable within twin pairs. However, the effects of cg06192883 were substantially attenuated within pairs. No change in DNA methylation was detected for any of the seven evaluated sites.Conclusion:Five of the seven sites investigated were associated with late-life level and/or change in BMI. The effects for four of the sites remained similar when examined within twin pairs, indicating that the associations are mainly environmentally driven. However, the substantial attenuation in the association between cg06192883 and late-life BMI within pairs points to the importance of genetic factors in this association.
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