• Other research productsclose
• 2019-2023close
• Open Access close
• European Commission close
• Wellcome Trust close
• EU close
• GB close
• English close

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD.

Introduction: Vaccines and drugs for the treatment and prevention of COVID-19 require robust evidence generated from clinical trials before they can be used. Decisions on how to apply non-pharmaceutical interventions such as quarantine, self-isolation, social distancing and travel restrictions should also be based on evidence. There are some experiential and mathematical modelling data for these interventions, but there is a lack of data on the social, ethical and behavioural aspects of these interventions in the literature. Therefore, our study aims to produce evidence to inform (non-pharmaceutical) interventions such as communications, quarantine, self-isolation, social distancing, travel restrictions and other public health measures for the COVID-19 pandemic. Methods: The study will be conducted in the United Kingdom, Italy, Malaysia, Slovenia and Thailand. We propose to conduct 600-1000 quantitative surveys and 25-35 qualitative interviews per country. Data collection will follow the following four themes: (1) Quarantine and self-isolation (2) social distancing and travel restrictions (3) wellbeing and mental health (4) information, misinformation and rumours. In light of limitations of travel and holding in-person meetings, we will primarily use online/remote methods for collecting data. Study participants will be adults who have provided informed consent from different demographic, socio-economic and risk groups. Discussion: At the time of the inception of the study, United Kingdom, Italy, Malaysia, Slovenia and Thailand have initiated strict public health measures and varying degrees of "lockdowns" to curb the pandemic. These public health measures will change in the coming weeks and months depending on the number of cases of COVID-19 in the respective countries. The data generated from our study could inform these strategies in real time.

The marine silicon cycle is intrinsically linked with carbon cycling in the oceans via biological production of silica by a wide range of organisms. The stable silicon isotopic composition (denoted by δ30Si) of siliceous microfossils extracted from sediment cores can be used as an archive of past oceanic silicon cycling. However, the silicon isotopic composition of biogenic silica has only been measured in diatoms, sponges and radiolarians, and isotopic fractionation relative to seawater is entirely unknown for many other silicifiers. Furthermore, the biochemical pathways and mechanisms that determine isotopic fractionation during biosilicification remain poorly understood. Here, we present the first measurements of the silicon isotopic fractionation during biosilicification by loricate choanoflagellates, a group of protists closely related to animals. We cultured two species of choanoflagellates, Diaphanoeca grandis and Stephanoeca diplocostata, which showed consistently greater isotopic fractionation (approximately −5 ‰ to −7 ‰) than cultured diatoms (−0.5 ‰ to −2.1 ‰). Instead, choanoflagellate silicon isotopic fractionation appears to be more similar to sponges grown under similar dissolved silica concentrations. Our results highlight that there is a taxonomic component to silicon isotope fractionation during biosilicification, possibly via a shared or related biochemical transport pathway. These findings have implications for the use of biogenic silica δ30Si produced by different silicifiers as proxies for past oceanic change.