To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations. One standard deviation increase of TL was associated with 0.021 unit increase (95% confidence interval [CI]: 0.001, 0.042) of standardized mean general cognitive ability. After controlling for sex, the point estimate remained similar (0.019) with a wider CI (95% CI: -0.002, 0.039). The association was attenuated with adjustment for educational attainment (0.009, 95% CI: -0.009, 0.028). No strong evidence was observed for the association of TL and decline in general cognitive ability. Longer TL was associated with higher general cognitive ability levels in the age-adjusted models but not in the models including all covariates, nor with cognitive decline.
Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR = 1.01, 95% CI 0.76-1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR = 0.80, 95% CI 0.61-1.03) and NSHDS cohorts (continuous RR = 0.73, 95% CI 0.54-0.97). The inverse association was also evident in the meta-analysis (continuous RR = 0.84, 95% CI 0.69-1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis.
Analysis of GLOBOCAN-2012 data shows clearly here that cancer incidence worldwide is highly related with low average annual temperatures and extreme low temperatures. This applies for all cancers together or separately for many frequent or rare cancer types (all cancers P?=?9.49×10-18). Supporting fact is that Inuit people, living at extreme low temperatures, have the highest cancer rates today. Hypothesizing an evolutionary explanation, 240 cancer genome-wide association studies, and seven genome-wide association studies for cold and high-altitude adaptation were combined. A list of 1,377 cancer-associated genes was created to initially investigate whether cold selected genes are enriched with cancer-associated genes. Among Native Americans, Inuit and Eskimos, the highest association was observed for Native Americans (P?=?6.7×10-5). An overall or a meta-analysis approach confirmed further this result. Similar approach for three populations living at extreme high altitude, revealed high association for Andeans-Tibetans (P?=?1.3×10-11). Overall analysis or a meta-analysis was also significant. A separate analysis showed special selection for tumor suppressor genes. These results can be viewed along with those of previous functional studies that showed that reduced apoptosis potential due to specific p53 variants (the most important tumor suppressor gene) is beneficial in high-altitude and cold environments. In conclusion, this study shows that genetic variants selected for adaptation at extreme environmental conditions can increase cancer risk later on age. This is in accordance with antagonistic pleiotropy hypothesis.
To analyse the accuracy of a meta-analysis-based dental age assessment (DAA) method in Finnish paediatric patients and to compare the dental development between two generations of Finnish children.
Panoramic radiographs of Finnish Caucasian healthy children from two generations (early: born 1981-1984; subsequent: born 1996-2008) were analysed. All developing teeth on the left maxilla and mandible as well as the third permanent molars were analysed following Demirjian's classification. For each patient, dental age was calculated and compared with chronological age. Dental maturation patterns between the two groups were compared.
The study included 200 Finnish Caucasian healthy children from two generations (early: aged 7-13 years; subsequent: aged 6-15 years). In the early generation, DAA underestimated the chronological age by a mean of 3.15 years. The underestimation was only 0.11 years in patients?
To describe and assess current effectiveness studies published up to 2014 using Swedish Prescribed Drug Register (SPDR) data.
Study characteristics were extracted. Each study was assessed concerning the clinical relevance of the research question, the risk of bias according to a structured checklist, and as to whether its findings contributed to new knowledge. The biases encountered and ways of handling these were retrieved.
A total of 24 effectiveness studies were included in the review, the majority on cardiovascular or psychiatric disease (n = 17; 71%). The articles linked data from four (interquartile range: three to four) registers, and were published in 21 different journals with an impact factor ranging from 1.58 to 51.66. All articles had a clinically relevant research question. According to the systematic quality assessments, the overall risk of bias was low in one (4%), moderate in eight (33%) and high in 15 (62%) studies. Overall, two (8%) studies were assessed as contributing to new knowledge. Frequently occurring problems were selection bias making the comparison groups incomparable, treatment bias with suboptimal handling of drug exposure and an intention-to-treat approach, and assessment bias including immortal time bias. Good examples of how to handle bias problems included propensity score matching and sensitivity analyses.
Although this review illustrates that effectiveness studies based on dispensed drug register data can contribute to new evidence of intended effects of drug treatment in clinical practice, the expectations of such data to provide valuable information need to be tempered due to methodological issues.
Cites: JAMA. 2014 Nov 19;312(19):2008-18 PMID 25399276
Tick-borne encephalitis (TBE) is one tick-transmitted disease where the human incidence has increased in some European regions during the last two decades. We aim to find the most important factors causing the increasing incidence of human TBE in Sweden. Based on a review of published data we presume that certain temperature-related variables and the population densities of transmission hosts, i.e. small mammals, and of primary tick maintenance hosts, i.e. cervids and lagomorphs, of the TBE virus vector Ixodes ricinus, are among the potentially most important factors affecting the TBE incidence. Therefore, we compare hunting data of the major tick maintenance hosts and two of their important predators, and four climatic variables with the annual numbers of human cases of neuroinvasive TBE. Data for six Swedish regions where human TBE incidence is high or has recently increased are examined by a time-series analysis. Results from the six regions are combined using a meta-analytical method.
With a one-year time lag, the roe deer (Capreolus capreolus), red deer (Cervus elaphus), mountain hare (Lepus timidus) and European hare (Lepus europaeus) showed positive covariance; the Eurasian elk (moose, Alces alces) and fallow deer (Dama dama) negative covariance; whereas the wild boar (Sus scrofa), lynx (Lynx lynx), red fox (Vulpes vulpes) and the four climate parameters showed no significant covariance with TBE incidence. All game species combined showed positive covariance.
The epidemiology of TBE varies with time and geography and depends on numerous factors, i.a. climate, virus genotypes, and densities of vectors, tick maintenance hosts and transmission hosts. This study suggests that the increased availability of deer to I. ricinus over large areas of potential tick habitats in southern Sweden increased the density and range of I. ricinus and created new TBEV foci, which resulted in increased incidence of human TBE. New foci may be established by TBE virus-infected birds, or by birds or migrating mammals infested with TBEV-infected ticks. Generally, persistence of TBE virus foci appears to require presence of transmission-competent small mammals, especially mice (Apodemus spp.) or bank voles (Myodes glareolus).
Alcohol consumption during pregnancy is sometimes associated with adverse outcomes in offspring, potentially mediated by epigenetic modifications. We aimed to investigate genome-wide DNA methylation in cord blood of newborns exposed to alcohol in utero.
We meta-analyzed information from six population-based birth cohorts within the Pregnancy and Childhood Epigenetics consortium.
We found no strong evidence of association at either individual CpGs or across larger regions of the genome.
Our findings suggest no association between maternal alcohol consumption and offspring cord blood DNA methylation. This is in stark contrast to the multiple strong associations previous studies have found for maternal smoking, which is similarly socially patterned. However, it is possible that a combination of a larger sample size, higher doses, different timings of exposure, exploration of a different tissue and a more global assessment of genomic DNA methylation might show evidence of association.
Cites: Alcohol. 2017 May;60:67-75 PMID 28187949
Cites: Int J Epidemiol. 2015 Aug;44(4):1083-93 PMID 26424516
Osteoarthritis has a highly negative impact on quality of life because of the associated pain and loss of joint function. Here we describe the largest meta-analysis so far of osteoarthritis of the hip and the knee in samples from Iceland and the UK Biobank (including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients, and more than 562,000 controls). We found 23 independent associations at 22 loci in the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for knee osteoarthritis. Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR)?=?2.8, P?=?7.9?×?10-12, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR?=?1.30, P?=?2.1?×?10-11, p.Arg112His). A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10-10, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm an association between hip osteoarthritis and a variant of CHADL1 (rs117018441, P = 1.8 × 10-25, OR = 5.9). Furthermore, we observe a complex relationship between height and risk of osteoarthritis.
Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes.
We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap).
We identified 30 GERD suggestive risk loci (P=5×10-5 ), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds.
We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.
High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults.
Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays.
Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P?