Assessing the associations between known genetic variants and substance use in people with HIV in the United States

Background The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH. Methods We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations. Results We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation. Conclusions Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Geneenvironment interactions (G x E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G x E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G x E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G x E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant GxBMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer

First Report of Stem Disease of Soybean (Glycine max) Caused by Diaporthe gulyae in North Dakota

The planted soybean (Glycine max L.) acreage in North Dakota increased approximately six-fold in the last two decades to over 6 million acres in 2016. In September 2012, soybean plants exhibiting reddish-brown stem cankers (∼60 mm length) were observed in a production field in Grand Forks county (49°11′N; 98°09′W). Incidence of infected stems was estimated in excess of 95% in parts of the field. Ten plants exhibiting symptoms were randomly sampled and brought to the Department of Plant Pathology at NDSU to identify the causal pathogen

Comparison of Greenhouse-Based Inoculation Methods to Study Aggressiveness of Diaporthe helianthi Isolates Causing Phomopsis Stem Canker of Sunflower (Helianthus annuus)

Phomopsis stem canker is an economically important disease of sunflower (Helianthus annuus), and Diaporthe helianthi is one of the primary causal agents of the disease in the United States. The objective of this study was to evaluate inoculation methods of D. helianthi isolates on sunflower in the greenhouse. Four isolates of D. helianthi were selected to test the effectiveness of four inoculation methods using mycelial plugs as the inoculum, including stem wound, wound inoculation, petiole wound, and straw test. Infection was established by the D. helianthi isolates at 14 days after inoculation for all inoculation methods used. However, recovery of the pathogen from the inoculated plants differed significantly (P \u3c 0.0001) among inoculation methods. Given higher mean recovery of D. helianthi isolates from the inoculated plants and the size of the lesions caused by the pathogen, the stem-wound inoculation method was found to be the most user friendly of the four inoculation methods

Why there Are no Earthquakes on the Marquesas Fracture Zone

Although the plate tectonic paradigm does not predict relative horizontal motion between lithosphere on opposing sides of a fracture zone, the fact that younger, more rapidly subsiding seafloor lies adjacent to older seafloor implies relative vertical motion. The observation that fracture zones are notably aseismic has led to the proposition of high strength along fracture zones, such that the differential subsidence is accommodated by flexure across a locked fault. This model predicts that a ridge develops on the young side of the fracture zone flanked by a foredeep trough on the old side, with parallel warping of the Moho and large associated gravity anomalies. Previous analyses of satellite altimetric passes over Pacific fracture zones have shown that the amplitude and shape of the gravity anomalies frequently do not conform to the predictions of this simple model. One of the most notable departures has been the Marquesas Fracture Zone (MFZ), where only one limited section was determined to be “high strength.” Curiously, the only earthquake to rupture the MFZ in the last 35 years is located in this locked region. Elsewhere, where we would predict vertical slip must be occurring, the fault is aseismic. To better understand the history of vertical motion on this fault, we have analyzed geophysical data obtained during the recent survey EW9106 aboard the R/V Maurice Ewing. Our detailed Hydrosweep, gravity, and seismic data resolve this paradox by showing no evidence for vertical slip along the fault. Shear stresses caused by differential thermal subsidence do not exceed the strength of this fault. Rather, the failure of the altimetry signal to conform to the predictions of the high-strength model along much of the MFZ is caused by changes in the Pacific-Farallon pole of rotation. Reorientation of the plate boundary was accommodated by propagating rifts, intratransform tension or compression, and changes in transform offset that complicated the signal from differential subsidence across a locked fault. For example, a counterclockwise rotation of the transform in the Cretaceous caused overthrusting in the transform and thus compensation of the depth differential by flexural loading of a very young plate. A clockwise rotation of this right-stepping transform fault at about 35 Ma led temporarily to a crenulated plate boundary and later to the development of intra-transform spreading centers. After accounting for these complications, the fracture zone appears capable of sustaining at least 20 MPa of shear stress and remains locked along the entire length of the fault except perhaps locally where it passed over the Tuamotu and Society hot spots

Phomopsis Stem Canker: A Reemerging Threat to Sunflower (Helianthus annuus) in the United States

Phomopsis stem canker causes yield reductions on sunflower (Helianthus annuus L.) on several continents, including Australia, Europe, and North America. In the United States, Phomopsis stem canker incidence has increased 16-fold in the Northern Great Plains between 2001 and 2012. Although Diaporthe helianthi was assumed to be the sole causal agent in the United States, a newly described species, D. gulyae, was found to be the primary cause of Phomopsis stem canker in Australia. To determine the identity of Diaporthe spp. causing Phomopsis stem canker in the Northern Great Plains, 275 infected stems were collected between 2010 and 2012. Phylogenetic analyses of sequences of the ribosomal DNA internal transcribed spacer region, elongation factor subunit 1-α, and actin gene regions of representative isolates, in comparison with those of type specimens, confirmed two species (D. helianthi and D. gulyae) in the United States. Differences in aggressiveness between the two species were determined using the stem-wound method in the greenhouse; overall, D. helianthi and D. gulyae did not vary significantly (P ≤ 0.05) in their aggressiveness at 10 and 14 days after inoculation. These findings indicate that both Diaporthe spp. have emerged as sunflower pathogens in the United States, and have implications on the management of this disease