Genetic Etiology of Parkinson Disease Associated with Mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 Genes: A Mutation Update

To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson-plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley-Liss, Inc

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Atmospheric composition in the European Arctic and 30 years of the Zeppelin Observatory, Ny-Ålesund

The Zeppelin Observatory (78.90°;N, 11.88°;E) is located on Zeppelin Mountain at 472 m a.s.l. on Spitsbergen, the largest island of the Svalbard archipelago. Established in 1989, the observatory is part of Ny-Ålesund Research Station and an important atmospheric measurement site, one of only a few in the high Arctic, and a part of several European and global monitoring programmes and research infrastructures, notably the European Monitoring and Evaluation Programme (EMEP); the Arctic Monitoring and Assessment Programme (AMAP); the Global Atmosphere Watch (GAW); the Aerosol, Clouds and Trace Gases Research Infrastructure (ACTRIS); the Advanced Global Atmospheric Gases Experiment (AGAGE) network; and the Integrated Carbon Observation System (ICOS). The observatory is jointly operated by the Norwegian Polar Institute (NPI), Stockholm University, and the Norwegian Institute for Air Research (NILU). Here we detail the establishment of the Zeppelin Observatory including historical measurements of atmospheric composition in the European Arctic leading to its construction. We present a history of the measurements at the observatory and review the current state of the European Arctic atmosphere, including results from trends in greenhouse gases, chlorofluorocarbons (CFCs) and hydrochlorofluorocarbons (HCFCs), other traces gases, persistent organic pollutants (POPs) and heavy metals, aerosols and Arctic haze, and atmospheric transport phenomena, and provide an outline of future research directions