Resource profile and user guide of the Polygenic Index Repository

Polygenic indexes (PGIs) are DNA-based predictors. Their value for research in many scientific disciplines is growing rapidly. As a resource for researchers, we used a consistent methodology to construct PGIs for 47 phenotypes in 11 datasets. To maximize the PGIs’ prediction accuracies, we constructed them using genome-wide association studies — some not previously published — from multiple data sources, including 23andMe and UK Biobank. We present a theoretical framework to help interpret analyses involving PGIs. A key insight is that a PGI can be understood as an unbiased but noisy measure of a latent variable we call the ‘additive SNP factor’. Regressions in which the true regressor is this factor but the PGI is used as its proxy therefore suffer from errors-in-variables bias. We derive an estimator that corrects for the bias, illustrate the correction, and make a Python tool for implementing it publicly available

SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors

Endocytic sorting of signalling receptors between recycling and degradative pathways is a key cellular process controlling the surface complement of receptors and, accordingly, the cell's ability to respond to specific extracellular stimuli. The β2 adrenergic receptor (β2AR) is a prototypical seven-transmembrane signalling receptor that recycles rapidly and efficiently to the plasma membrane after ligand-induced endocytosis. β2AR recycling is dependent on the receptor's carboxy-terminal PDZ ligand and Rab4. This active sorting process is required for functional resensitization of β2AR-mediated signalling. Here we show that sequence-directed sorting occurs at the level of entry into retromer tubules and that retromer tubules are associated with Rab4. Furthermore, we show that sorting nexin 27 (SNX27) serves as an essential adaptor protein linking β2ARs to the retromer tubule. SNX27 does not seem to directly interact with the retromer core complex, but does interact with the retromer-associated Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. The present results identify a role for retromer in endocytic trafficking of signalling receptors, in regulating a receptor-linked signalling pathway, and in mediating direct endosome-to-plasma membrane traffic

Decreased postural control in adolescents born with extremely low birth weight

This is an accepted manuscript of an article published by Springer in Experimental Brain Research on 14 March 2015, available online: https://doi.org/10.1007/s00221-015-4239-3 The accepted version of the publication may differ from the final published version.The survival rates of infants born preterm with extremely low birth weight (ELBW ≤ 1000 g) have gradually improved over the last decades. However, these infants risk to sustain long-term disorders related to poor neurodevelopment. The objective was to determine whether adolescents born with ELBW have decreased postural control and stability adaptation. Twenty-nine ELBW subjects performed posturography with eyes open and closed under unperturbed and perturbed standing by repeated calf vibration. Their results were compared with twenty-one age- and gender-matched controls born after full-term pregnancy. The ELBW group had significantly decreased stability compared with controls in anteroposterior direction, both during the easier quiet stance posturography (p = 0.007) and during balance perturbations (p = 0.007). The ELBW group had similar stability decrease in lateral direction during balance perturbations (p = 0.013). Statistically, the stability decreases were similar with eyes closed and open, but proportionally larger with eyes open in both directions. Both groups manifested significant adaptation (p ≤ 0.023) to the balance perturbations in anteroposterior direction, though this adaptation process could not compensate for the general stability deficits caused by ELBW on postural control. Hence, adolescent survivors of ELBW commonly suffer long-term deficits in postural control, manifested as use of substantially more recorded energy on performing stability regulating high-frequency movements and declined stability with closed and open eyes both in anteroposterior and lateral direction. The determined relationship between premature birth and long-term functional deficits advocates that interventions should be developed to provide preventive care in neonatal care units and later on in life.Published versio

Publisher Correction: Brain charts for the human lifespan.

In the version of this article initially published, there were errors in the affiliations for K. Im (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), J. Lerch (missing affiliation, Mouse Imaging Centre, Toronto, Ontario, Canada), S. Villeneuve and X. N. Zuo (incorrect affiliation numbers listed), H. Yun (missing affiliation, Division of Newborn Medicine and Neuroradiology, Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA), and H. J. Zar (extra affiliation shown). In addition, the affiliation numbers for all authors listed in the consortium membership section were incorrect by 1–3 digits. The errors have been corrected in the HTML and PDF versions of the article