Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Intelligence is associated with important economic and health-related life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3,4,5. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10−8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10−6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10−6). Despite the well-known difference in twin-based heritability2 for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10−29). These findings provide new insight into the genetic architecture of intelligence

Microfabrication and characterization of a silicon-based millimeter scale, PEM fuel cell operating with hydrogen, methanol, or formic acid

A silicon-based microfabricated fuel cell has been developed to provide a high energy and power density power source on the millimeter size scale. An integrated silicon microscale membrane electrode assembly (Si-μMEA) consisting of a Nafion 112™ membrane bonded between two electrodes on microstructured silicon substrates forms the core element of this polymer electrolyte membrane fuel cell. The use of silicon meshes that serve the purpose of catalyst support, current collector, and structural element provides a promising alternative to the traditional gas diffusion layer-based MEAs for the development of robust, high-performance microfuel cells. The cell performance was characterized using hydrogen, methanol, and concentrated formic acid–water fuels at the anode, and oxygen at the cathode. The catalyst used for each fuel was Pt black. Preliminary results show that the microfabricated fuel cell running on formic acid may be a promising alternative for fuel cell applications running at ambient temperature and pressure, provided additional work on catalyst improvement, assembly, and packaging is performed so that the power density achieves that of traditional forced fed PEM fuel cell design. © 2004 Elsevier B.V. All rights reserved

Investigation of Complement Component <i>C4</i> Copy Number Variation in Human Longevity

<div><p>Genetic factors have been estimated to account for about 25% of the variation in an adult's life span. The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the overall <i>C4</i> copy number or gene size (long <i>C4L</i>; short <i>C4S</i>) may influence the strength of the immune response and disease susceptibilities. Previously, an association between <i>C4B</i> copy number and life span was reported for Hungarians and Icelanders, where the <i>C4B*Q0</i> genotype, which is defined by <i>C4B</i> gene deficiency, showed a decrease in frequency with age. Additionally, one of the studies indicated that a low <i>C4B</i> copy number might be a genetic trait that is manifested only in the presence of the environmental risk factor “smoking”. These observations prompted us to investigate the role of the <i>C4</i> alleles in our large German longevity sample (∼700 cases; 94–110 years and ∼900 younger controls). No significant differences in the number of <i>C4A</i>, <i>C4B</i> and <i>C4S</i> were detected. Besides, the <i>C4B*Q0</i> carrier state did not decrease with age, irrespective of smoking as an interacting variable. However, for <i>C4L*Q0</i> a significantly different carrier frequency was observed in the cases compared with controls (cases: 5.08%; controls: 9.12%; p = 0.003). In a replication sample of 714 German cases (91–108 years) and 890 controls this result was not replicated (p = 0.14) although a similar trend of decreased <i>C4L*Q0</i> carrier frequency in cases was visible (cases: 7.84%; controls: 10.00%).</p></div

Centrifugal Sedimentation for Selectively Packing Channels with Silica Microbeads in Three-Dimensional Micro/Nanofluidic Devices

Incorporation of nanofluidic elements into microfluidic channels is one approach for adding filtration and partition functionality to planar microfluidic devices, as well as providing enhanced biomolecular separations. Here we introduce a strategy to pack microfluidic channels with silica nanoparticles and microbeads, thereby indirectly producing functional nanostructures; the method allows selected channels to be packed, here demonstrated so that a separation channel is packed while keeping an injection channel unpacked. A nanocapillary array membrane is integrated between two patterned microfluidic channels that cross each other in vertically separated layers. The membrane serves both as a hit for bead packing and as a fluid communication conduit between microfluidic channels. Centrifugal force-assisted sedimentation is then used to selectively pack the microfluidic channels using an aqueous silica bead suspension loaded into the appropriate inlet reservoirs. This packing approach may be used to simultaneously pack multiple channels with silica microbeads having different sizes and surface properties. The chip design and packing method introduced here are suitable for packing silica particles in sizes ranging from nanometers to micrometers and allow rapid (similar to 10 min) packing with high quality. The liquid/analyte transport characteristics of these packed micro/nanofluidic devices have potential utility in a wide range of applications, including electroosmotic pumping, liquid chromatographic separations, and electrochromatography