Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia

Myopia, or nearsightedness, is the most common eye disorder, resulting primarily from excess elongation of the eye. The etiology of myopia, although known to be complex, is poorly understood. Here we report the largest ever genome-wide association study (43,360 participants) on myopia in Europeans. We performed a survival analysis on age of myopia onset and identified 19 significant associations (p < 5e-8), two of which are replications of earlier associations with refractive error. These 19 associations in total explain 2.7% of the variance in myopia age of onset, and point towards a number of different mechanisms behind the development of myopia. One association is in the gene PRSS56, which has previously been linked to abnormally small eyes; one is in a gene that forms part of the extracellular matrix (LAMA2); two are in or near genes involved in the regeneration of 11-cis-retinal (RGR and RDH5); two are near genes known to be involved in the growth and guidance of retinal ganglion cells (ZIC2, SFRP1); and five are in or near genes involved in neuronal signaling or development. These novel findings point towards multiple genetic factors involved in the development of myopia and suggest that complex interactions between extracellular matrix remodeling, neuronal development, and visual signals from the retina may underlie the development of myopia in humans

An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma

The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer

Efficient Replication of Over 180 Genetic Associations with Self-Reported Medical Data

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for amassing large amounts of medical information in a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggests that online collection of self-reported data in a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations

Corrigendum to “Pollen-based paleoenvironmental and paleoclimatic change at Lake Ohrid (south-eastern Europe) during the past 500 ka” published in Biogeosciences, 13, 1423–1437, 2016

In this corrigendum we report an updated pollen record from the Lake Ohrid DEEP site spanning the past 500 ka whereby we have reprocessed and re-analyzed 104 samples affected by chemical procedure problems that occurred in one palynological laboratory. Firstly, these samples were affected by the use of wrong containers, causing in- adequate settling of particles at the set centrifuging speed. Secondly, HCl and HF treatments were combined without the prescribed intermediate centrifuging and decanting steps. The inaccuracy in the protocol resulted in the loss of smaller pollen grains and in the overrepresentation of bisaccate ones in most of the re-analyzed samples. We therefore provide an updated set of figures with the new data and have revised the description of the results, discussion and conclusions re- ported in Sadori et al. (2016) where necessary. We stress that the majority of the original results and conclusions remain valid, while the records’ reliability and resolution have improved as 12 samples that had been omitted in the original study because of low count sums are now included in the revised dataset (Sadori et al., 2018)

Gravity optimised particle filter for hand tracking

This paper presents a gravity optimised particle filter (GOPF) where the magnitude of the gravitational force for every particle is proportional to its weight. GOPF attracts nearby particles and replicates new particles as if moving the particles towards the peak of the likelihood distribution, improving the sampling efficiency. GOPF is incorporated into a technique for hand features tracking. A fast approach to hand features detection and labelling using convexity defects is also presented. Experimental results show that GOPF outperforms the standard particle filter and its variants, as well as state-of-the-art CamShift guided particle filter using a significantly reduced number of particles