Variation in complement factor 3 is associated with risk of age-related macular degeneration

The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.     

Cryptic subarctic diversity: a new bumblebee species from the Yukon and Alaska (Hymenoptera: Apidae)

It is nearly 90 years since a bumblebee species has been described for the first time from Canada or the USA that was previously unrecognised by science. We describe and illustrate Bombus(Alpinobombus) kluanensis sp. nov. and begin to map its distribution. This species was discovered through analysis of Cytochrome c Oxidase subunit I barcodes and had been unsuspected on the basis of morphological and colour characteristics. So far, 247 female specimens considered to belong to this species are known from the subarctic mountains associated with the Denali Fault running from the Alaska Range (Alaska, USA) to Kluane in the Saint Elias Mountains (Yukon, Canada). A checklist of all species of the subgenus Alpinobombus worldwide is provided.

http://zoobank.org/urn:lsid:zoobank.org:pub:78D524DD-FFBA-4BC4-8D39-3EF4F6BDD39E     

On the Difficulty of Measuring Forecasting Skill in Financial Markets

The use of correlation between forecasts and actual returns is commonplace in the literature, often used as a measurement of investors' skill. A prominent application of this is the concept of the information coefficient (IC). Not only can the IC be used as a tool to rate analysts and fund managers but it also represents an important parameter in the asset allocation and portfolio construction process. Nevertheless, a theoretical understanding of it has typically been limited to the partial equilibrium context where the investing activities of each agent have no effect on other market participants. In this paper we show that this can be an undesirable oversimplification and we demonstrate plausible circumstances in which conventional empirical measurements of IC can be highly misleading. We suggest that improved understanding of IC in a general equilibrium setting can lead to refined portfolio decision making ex ante and more informative analysis of performance ex post. Copyright © 2015 John Wiley & Sons, Ltd.     

A new species of Schizopera (Copepoda: Harpacticoida) from Japan,its phylogeny based on the mtCOI gene and comments on the genus Schizoperopsis

The predominantly marine genus Schizopera Sars, 1905 has only two significant inland water species-flocks, one in the ancient African Lake Tanganyika and the other in subterranean waters of Western Australia. Discovery of Schizopera abei sp. nov. from several interstitial locations in the vicinity of the ancient Lake Biwa has wider implications for the study of morphological homoplasies in the genus, as well as for the study of freshwater invasions in harpacticoid copepods. The new Schizopera species belongs to a small group of congeners with a two-segmented endopod of the fourth leg, which used to be recognised as a separate genus, Schizoperopsis Apostolov, 1982. Our reconstructed phylogenies based on the mtCOI partial sequences suggest that this character probably evolved convergently in at least some Schizopera, thus rendering the genus Schizoperopsis polyphyletic. However, almost all basal nodes in our cladograms are weakly supported, which shows limitations of a single-gene approach for reconstructing phylogenetic relationships. The new species is the first member of its genus from Japanese inland waters, and it has no close relatives among extent congeners anywhere in the world. We speculate that its ancestor may have invaded Lake Biwa, and subsequently its surrounding subterranean waters, from brackish areas around central Japan, presumably during a period of high sea water level through its major outflow river. This discovery may provide further support for the hypothesis about the role of ancient lakes as biodiversity pumps for subterranean habitats.

http://zoobank.org/urn:lsid:zoobank.org:pub:1F71F7AD-B7C8-4AD3-BE44-5E1BEE4E2AA8     

Inference to the hypothesis of extended cognition

This paper examines the justification for the hypothesis of extended cognition (HEC). HEC claims that human cognitive processes can, and often do, extend outside our head to include objects in the environment. HEC has been justified by inference to the best explanation (IBE). Both advocates and critics of HEC claim that we can infer the truth value of HEC based on whether HEC makes a positive or negative explanatory contribution to cognitive science. I argue that IBE cannot play this epistemic role. A serious rival to HEC exists with a differing truth value, and this invalidates IBEs for both the truth and the falsity of HEC. Explanatory value to cognitive science is not a guide to the truth value of HEC.     

Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.     

PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans

Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.     

Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits

We present an approximate conditional and joint association analysis that can use summary-level statistics from a meta-analysis of genome-wide association studies (GWAS) and estimated linkage disequilibrium (LD) from a reference sample with individual-level genotype data. Using this method, we analyzed meta-analysis summary data from the GIANT Consortium for height and body mass index (BMI), with the LD structure estimated from genotype data in two independent cohorts. We identified 36 loci with multiple associated variants for height (38 leading and 49 additional SNPs, 87 in total) via a genome-wide SNP selection procedure. The 49 new SNPs explain approximately 1.3% of variance, nearly doubling the heritability explained at the 36 loci. We did not find any locus showing multiple associated SNPs for BMI. The method we present is computationally fast and is also applicable to case-control data, which we demonstrate in an example from meta-analysis of type 2 diabetes by the DIAGRAM Consortium.     

Extremely low-coverage sequencing and imputation increases power for genome-wide association studies

Genome-wide association studies (GWAS) have proven to be a powerful method to identify common genetic variants contributing to susceptibility to common diseases. Here, we show that extremely low-coverage sequencing (0.1-0.5×) captures almost as much of the common (>5%) and low-frequency (1-5%) variation across the genome as SNP arrays. As an empirical demonstration, we show that genome-wide SNP genotypes can be inferred at a mean r(2) of 0.71 using off-target data (0.24× average coverage) in a whole-exome study of 909 samples. Using both simulated and real exome-sequencing data sets, we show that association statistics obtained using extremely low-coverage sequencing data attain similar P values at known associated variants as data from genotyping arrays, without an excess of false positives. Within the context of reductions in sample preparation and sequencing costs, funds invested in extremely low-coverage sequencing can yield several times the effective sample size of GWAS based on SNP array data and a commensurate increase in statistical power.     

Common variants at 12q14 and 12q24 are associated with hippocampal volume

Aging is associated with reductions in hippocampal volume that are accelerated by Alzheimer's disease and vascular risk factors. Our genome-wide association study (GWAS) of dementia-free persons (n = 9,232) identified 46 SNPs at four loci with P values of <4.0 × 10(-7). In two additional samples (n = 2,318), associations were replicated at 12q14 within MSRB3-WIF1 (discovery and replication; rs17178006; P = 5.3 × 10(-11)) and at 12q24 near HRK-FBXW8 (rs7294919; P = 2.9 × 10(-11)). Remaining associations included one SNP at 2q24 within DPP4 (rs6741949; P = 2.9 × 10(-7)) and nine SNPs at 9p33 within ASTN2 (rs7852872; P = 1.0 × 10(-7)); along with the chromosome 12 associations, these loci were also associated with hippocampal volume (P < 0.05) in a third younger, more heterogeneous sample (n = 7,794). The SNP in ASTN2 also showed suggestive association with decline in cognition in a largely independent sample (n = 1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8) and neuronal migration (ASTN2), as well as enzymes targeted by new diabetes medications (DPP4), indicating new genetic influences on hippocampal size and possibly the risk of cognitive decline and dementia.