Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Concordance between digital pathology and light microscopy in general surgical pathology: A pilot study of 100 cases

Aim (1)
A pilot study to determine the accuracy of interpretation of whole slide digital images in a broad range of general histopathology cases of graded complexity. (2) To survey the participating histopathologists with regard to acceptability of digital pathology.

Materials and methods
Glass slides of 100 biopsies and minor resections were digitally scanned in their entirety, producing digital slides. These cases had been diagnosed by light microscopy at least 1 year previously and were subsequently reassessed by the original reporting pathologist (who was blinded to their original diagnosis) using digital pathology. The digital pathology-based diagnosis was compared with the original glass slide diagnosis and classified as concordant, slightly discordant (without clinical consequence) or discordant. The participants were surveyed at the end of the study.

Results
There was concordance between the original light microscopy diagnosis and digital pathology-based diagnosis in 95 of the 100 cases while the remaining 5 cases showed only slight discordance (with no clinical consequence). None of the cases were categorised as discordant. Participants had mixed experiences using digital pathology technology.

Conclusions
In the broad range of cases we examined, digital pathology is a safe and viable method of making a primary histopathological diagnosis.

The distribution of COPD in UK general practice using the new GOLD classification

The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 document recommends a combined assessment of chronic obstructive pulmonary disease (COPD) based on current symptoms and future risk.

A large database of primary-care COPD patients across the UK was used to determine COPD distribution and characteristics according to the new GOLD classification. 80 general practices provided patients with a Read code diagnosis of COPD. Electronic and hand searches of patient medical records were undertaken, optimising data capture.

Data for 9219 COPD patients were collected. For the 6283 patients with both forced expiratory volume in 1 s (FEV1) and modified Medical Research Council scores (mean¡SD age 69.2¡10.6 years, body mass index 27.3¡6.2 kg?m-2), GOLD 2011 group distributions were: A (low risk and fewer symptoms) 36.1%, B (low risk and more symptoms) 19.1%, C (high risk and fewer symptoms) 19.6% and D (high risk and more symptoms) 25.3%. This is in contrast with GOLD 2007 stage classification: I (mild) 17.1%, II (moderate) 52.2%, III (severe) 25.5% and IV (very severe) 5.2%. 20% of patients with FEV1 o50% predicted had more than two exacerbations in the previous 12 months. 70% of patients with FEV1 ,50% pred had fewer than two exacerbations in the previous 12 months.

This database, representative of UK primary-care COPD patients, identified greater proportions of patients in the mildest and most severe categories upon comparing 2011 versus 2007 GOLD classifications. Discordance between airflow limitation severity and exacerbation risk was observed.

General practice-recorded depression and antidepressant use in young people with newly diagnosed Type 1 diabetes: a cohort study using the Clinical Practice Research Datalink

Aims - To investigate whether young people with Type 1 diabetes have an increased rate of depression andantidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period ofdiagnosis or complications status. Methods - A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) wasidentified within the Clinical Practice Research Datalink and individually age and sex matched with up to two controlsubjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recordeddepression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in peoplewith Type 1 diabetes compared with control subjects. Results - People with Type 1 diabetes were twice as likely to have a record of antidepressant use and generalpractice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73–2.50, P < 0.001).These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis(hazard ratio 2.14, 95% CI 1.51–3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10-to 19-year age group (hazard ratio 1.45, 95% CI 1.06–1.98, P = 0.02). Conclusions - This population-based study shows that people with Type 1 diabetes have higher rates of generalpractice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis,suggesting psychological input for patients is warranted in the early years of their condition.