University of Gothenburg

About: University of Gothenburg is a education organization based out in Gothenburg, Sweden. It is known for research contribution in the topics: Population & Health care. The organization has 23855 authors who have published 65241 publications receiving 2606327 citations. The organization is also known as: Göteborg University & Gothenburg University.

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

Abstract: The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano–Monghidoro study

Abstract: OBJECTIVE Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. METHODS 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). RESULTS The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett's oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett's oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett's oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. CONCLUSIONS GORD is common in Italy, but the prevalence of Barrett's oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett's oesophagus often have no reflux symptoms.

Indices for daily temperature and precipitation extremes in Europe analyzed for the period 1901–2000

Abstract: [1] We analyze century-long daily temperature and precipitation records for stations in Europe west of 60°E. A set of climatic indices derived from the daily series, mainly focusing on extremes, is defined. Linear trends in these indices are assessed over the period 1901–2000. Average trends, for 75 stations mostly representing Europe west of 20°E, show a warming for all temperature indices. Winter has, on average, warmed more (∼1.0°C/100 yr) than summer (∼0.8°C), both for daily maximum (TX) and minimum (TN) temperatures. Overall, the warming of TX in winter was stronger in the warm tail than in the cold tail (1.6 and 1.5°C for 98th and 95th, but ∼1.0°C for 2nd, 5th and 10th percentiles). There are, however, large regional differences in temperature trend patterns. For summer, there is a tendency for stronger warming, both for TX and TN, in the warm than in the cold tail only in parts of central Europe. Winter precipitation totals, averaged over 121 European stations north of 40°N, have increased significantly by ∼12% per 100 years. Trends in 90th, 95th and 98th percentiles of daily winter precipitation have been similar. No overall long-term trend occurred in summer precipitation totals, but there is an overall weak (statistically insignificant and regionally dependent) tendency for summer precipitation to have become slightly more intense but less common. Data inhomogeneities and relative sparseness of station density in many parts of Europe preclude more robust conclusions. It is of importance that new methods are developed for homogenizing daily data.

Plasma β-amyloid in Alzheimer’s disease and vascular disease

Abstract: Implementation of amyloid biomarkers in clinical practice would be accelerated if such biomarkers could be measured in blood. We analyzed plasma levels of Aβ42 and Aβ40 in a cohort of 719 individuals (the Swedish BioFINDER study), including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia and cognitively healthy elderly, using a ultrasensitive immunoassay (Simoa platform). There were weak positive correlations between plasma and cerebrospinal fluid (CSF) levels for both Aβ42 and Aβ40, and negative correlations between plasma Aβ42 and neocortical amyloid deposition (measured with PET). Plasma levels of Aβ42 and Aβ40 were reduced in AD dementia compared with all other diagnostic groups. However, during the preclinical or prodromal AD stages (i.e. in amyloid positive controls, SCD and MCI) plasma concentration of Aβ42 was just moderately decreased whereas Aβ40 levels were unchanged. Higher plasma (but not CSF) levels of Aβ were associated with white matter lesions, cerebral microbleeds, hypertension, diabetes and ischemic heart disease. In summary, plasma Aβ is overtly decreased during the dementia stage of AD indicating that prominent changes in Aβ metabolism occur later in the periphery compared to the brain. Further, increased levels of Aβ in plasma are associated with vascular disease.