To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 10(-8)), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.

Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case-control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case-control populations, we found that a SNP in alpha-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0 x 10(-10)). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D'>0.9) spanning approximately 120 kb. A tight LD group (r2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0 x 10(-9)-1.7 x 10(-11)). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated with the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.

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X-ray spectroscopy is an important tool for understanding the extreme photoionization processes that drive the behaviour of non-thermal equilibrium plasmas in compact astrophysical objects such as black holes 1-4. Even so, the distance of these objects from the Earth and the inability to control or accurately ascertain the conditions that govern their behaviour makes it difficult to interpret the origin of the features in astronomical X-ray measurements. Here, we describe an experiment that uses the implosion 5 driven by a 3 TW, 4 kJ laser system 6 to produce a 0.5 keV blackbody radiator that mimics the conditions that exist in the neighbourhood of a black hole. The X-ray spectra emitted from photoionized silicon plasmas resemble those observed from the binary stars Cygnus X-3 (refs 7, 8) and Vela X-1 (refs 9-11) with the Chandra X-ray satellite. As well as demonstrating the ability to create extreme radiation fields in a laboratory plasma, our theoretical interpretation of these laboratory spectra contrasts starkly with the generally accepted explanation for the origin of similar features in astronomical observations. Our experimental approach offers a powerful means to test and validate the computer codes used in X-ray astronomy. X-ray spectroscopy with an X-ray satellite is the main observational method to give information about compact objects, especially black holes. Black holes are indirectly studied by observing the X-ray continuum from a heated accretion disc and the X-ray fluorescence from the ambient gas of the stellar wind and the surface of a companion star in their binary systems. To derive physical properties from the observations, X-ray astronomers rely on non-local-thermodynamical-equilibrium (LTE) atomic physics in a cold ambient gas subject to an extreme radiation field, for which the mean radiation temperature is of the order of 1 keV. Theoretical models have been developed on the basis of the observed spectra 1-4 and complex computer codes were developed to analyse the observed X-ray spectra 12-16. The underlying assumption of these models is that the spectrum originates from a photoionized plasma. In other words, the intense radiation from the compact object photoionizes the gas, and generates a relatively low-electron-temperature highly ionized non-LTE plasma. However, laboratory experiments on non-LTE photoionized plasmas