BackgroundGenomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.MethodsWe analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons).Results and conclusionsMany of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV–phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers.

BackgroundCopy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them have been associated with changes in weight, height, and other physical traits. As most studies have been performed on children and young people, these effects of CNVs in middle-aged and older people are not well established. The UK Biobank recruited half a million adults who provided a variety of physical measurements. We called all CNVs from the Affymetrix microarrays and selected a set of 54 CNVs implicated as pathogenic (including their reciprocal deletions/duplications) and that were found in five or more persons. Linear regression analysis was used to establish their association with 16 physical traits relevant to human health.Results396,725 participants of white British or Irish descent (excluding first-degree relatives) passed our quality control filters. Out of the 864 CNV/trait associations, 214 were significant at a false discovery rate of 0.1, most of them novel. Many of these traits increase risk for adverse health outcomes: e.g. increases in weight, waist-to-hip ratio, pulse rate and body fat composition. Deletions at 16p11.2, 16p12.1, NRXN1 and duplications at 16p13.11 and 22q11.2 produced the highest numbers of significant associations. Five CNVs produced average changes of over one standard deviation for the 16 traits, compared to controls: deletions at 16p11.2 and 22q11.2, and duplications at 3q29, the Williams-Beuren and Potocki-Lupski regions. CNVs at 1q21.1, 2q13, 16p11.2 and 16p11.2 distal, 16p12.1, 17p12 and 17q12 demonstrated one or more mirror image effects of deletions versus duplications.ConclusionsCarriers of many CNVs should be monitored for physical traits that increase morbidity and mortality. Genes within these CNVs can give insights into biological processes and therapeutic interventions.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5292-7) contains supplementary material, which is available to authorized users.

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Background. Copy number variants (CNVs) have been shown to increase risk for physical

The validity of clinical decision making in homeopathy is largely unexplored and little is understood about the process or its reliability. This exploratory study investigated, in the context of a questionnaire based re-proving of Belladonna 30c, the extent to which decisions are based on clinical facts or intuition and how reliable decisions are. Three experienced, independent homeopathic clinicians/proving researchers rated the symptom diaries of the 206 subjects taking part. They reported their proving decision (ie positive proving response, no proving response or undecided) based on the total symptom profiles and rated (on a scale of 0-10) their use of clinical facts or intuition. Keynote symptoms and overall confidence scores were also reported. The level of agreement between raters was generally poor (weighted kappa 0.349-0.064). All raters used both facts and intuition. The rater's reliance on the facts was significantly associated with classifying those subjects who had no proving response [rater 1, P<0.001; rater 2, P<0.001]. Raters used significantly higher intuition scores when classifying a prover [rater 2, P= 0.001; rater 3, P= 0.012]. Issues regarding the education and practice of homeopathy are discussed.