Genome-wide association study reveals three susceptibility loci for common migraine in the general population

Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 × 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 × 10(-9); rs10166942, OR = 0.85, P = 5.5 × 10(-12); and rs11172113, OR = 0.90, P = 4.3 × 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.     

Note on occurrence of Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) in Montana: a new state record

The parasitic wasp Mymaromella pala Huber and Gibson (Hymenoptera: Mymarommatidae) was collected at 4 sites within a canyon reach of the Kootenai River in Lincoln County, Montana. This minute species has only recently been described, but it appears to have a large distribution throughout the United States and to be associated with upland and riparian forests. La avispa parasitaria Mymaromella pala Huber y Gibson (Hymenoptera: Mymarommatidae) se recolect&oacute; en cuatro sitios a lo largo de un ca&ntilde;&oacute;n del R&iacute;o Kootenai en Lincoln Co., MT. Hace poco que se describi&oacute; esta especie diminuta, pero parece tener una distribuci&oacute;n extensa en los EE.UU. y estar asociada con bosques altos y ribere&ntilde;os.     

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.     

Expression and characterization of the cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis (CF) is a common lethal genetic disease that manifests itself in airway and other epithelial cells as defective chloride ion absorption and secretion, resulting at least in part from a defect in a cyclic AMP-regulated, outwardly-rectifying Cl- channel in the apical surface. The gene responsible for CF has been identified and predicted to encode a membrane protein termed the CF transmembrane conductance regulator (CFTR). Identification of a cryptic bacterial promoter within the CFTR coding sequence led us to construct a complementary DNA in a low-copy-number plasmid, thereby avoiding the deleterious effects of CFTR expression on Escherischia coli. We have used this cDNA to express CFTR in vitro and in vivo. Here we demonstrate that CFTR is a membrane-associated glycoprotein that can be phosporylated in vitro by cAMP-dependent protein kinase. Polyclonal and monoclonal antibodies directed against distinct domains of the protein immunoprecipitated recombinant CFTR as well as the endogenous CFTR in nonrecombinant T84 cells. Partial proteolysis fingerprinting showed that the recombinant and non-recombinant proteins are indistinguishable. These data, which establish several characteristics of the protein responsible for CF, will now enable CFTR function to be studied and will provide a basis for diagnosis and therapy.     

The role of parasites in sympatric and allopatric host diversification

Exploiters (parasites and predators) are thought to play a significant role in diversification, and ultimately speciation, of their hosts or prey. Exploiters may drive sympatric (within-population) diversification if there are a variety of exploiter-resistance strategies or fitness costs associated with exploiter resistance. Exploiters may also drive allopatric (between-population) diversification by creating different selection pressures and increasing the rate of random divergence. We examined the effect of a virulent viral parasite (phage) on the diversification of the bacterium Pseudomonas fluorescens in spatially structured microcosms. Here we show that in the absence of phages, bacteria rapidly diversified into spatial niche specialists with similar patterns of diversity across replicate populations. In the presence of phages, sympatric diversity was greatly reduced, as a result of phage-imposed reductions in host density decreasing competition for resources. In contrast, allopatric diversity was greatly increased as a result of phage-imposed selection for resistance, which caused populations to follow divergent evolutionary trajectories. These results show that exploiters can drive diversification between populations, but may inhibit diversification within populations by opposing diversifying selection that arises from resource competition.     

Respiration in the open ocean

A key question when trying to understand the global carbon cycle is whether the oceans are net sources or sinks of carbon. This will depend on the production of organic matter relative to the decomposition due to biological respiration. Estimates of respiration are available for the top layers, the mesopelagic layer, and the abyssal waters and sediments of various ocean regions. Although the total open ocean respiration is uncertain, it is probably substantially greater than most current estimates of particulate organic matter production. Nevertheless, whether the biota act as a net source or sink of carbon remains an open question.