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.     

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.     

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.     

长白山采集的中国东北新记录苔藓植物

在对中国和加拿大苔藓学者联合于中国东北最高的长白山采集的2千余份标本鉴定的基础上。认定有苔藓植物59科，152属，300种。报道了中国大陆新记录1属－小曲柄藓属（Campylostelium）。中国东北新记录2属－直蓑衣藓属（Macrocoma）和同叶藓属（Isopterygium）。中国东北新记录5种－褶叶裂叶苔（Lophozia incisa）。假狗牙藓（Cynodontium fallax）。细枝牛毛藓（Ditrichum gracile）。散叶牛毛藓（Ditrichum divarcatum）和细叶棉藓（Plagiothecium latebricola）。     

On the ultrastructure of mammalian tendon

Zusammenfassung Es wird gezeigt, dass die zwischen gekreuzten Nicols für die Rattenschwanzsehne nachgewiesenen periodischen Bänder von fibrillären Strukturelementen ebener Wellenform abstammen und deren Ausstreckung das beobachtete Dehnungsverhalten erklärt², das auch für andere Säugetiere zutrifft.     

Adrenal lipid and plasma corticosterone depletion after 7,12-dimethylbenz(a)anthracene administration to the albino rat

Zusammenfassung Fluorometrische Messungen zeigten eine Abnahme von Plasmacorticosterone (CCS). Die Bedeutung dieser Resultate für theoretische Aspekte der Karzinogenese wird diskutiert.     

Fire-induced erosion and millennial-scale climate change in northern ponderosa pine forests

Western US ponderosa pine forests have recently suffered extensive stand-replacing fires followed by hillslope erosion and sedimentation. These fires are usually attributed to increased stand density as a result of fire suppression, grazing and other land use, and are often considered uncharacteristic or unprecedented. Tree-ring records from the past 500 years indicate that before Euro-American settlement, frequent, low-severity fires maintained open stands. However, the pre-settlement period between about ad 1500 and ad 1900 was also generally colder than present, raising the possibility that rapid twentieth-century warming promoted recent catastrophic fires. Here we date fire-related sediment deposits in alluvial fans in central Idaho to reconstruct Holocene fire history in xeric ponderosa pine forests and examine links to climate. We find that colder periods experienced frequent low-severity fires, probably fuelled by increased understory growth. Warmer periods experienced severe droughts, stand-replacing fires and large debris-flow events that comprise a large component of long-term erosion and coincide with similar events in sub-alpine forests of Yellowstone National Park. Our results suggest that given the powerful influence of climate, restoration of processes typical of pre-settlement times may be difficult in a warmer future that promotes severe fires.