Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and ...interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
Potato mop-top virus (PMTV) is the type member of the genus Pomovirus. PMTV is an important pathogen of potato, causing significant economic losses in Northern Europe, North and South America, and ...Asia (3). PMTV in the United States was first reported in Maine (2). PMTV is vectored by the plasmodiophoromycete Spongospora subterranea cv. subterranea, which causes powdery scab of potato (1). S. subterranea and PMTV are usually associated with cool and humid environments. In the spring of 2010, six potato tubers of cv. Russet Burbank were received from a commercial potato farm in Grand Forks County in North Dakota. The tubers had multiple, internal, concentric, necrotic arcs and circles. The presence of PMTV in the necrotic lesions was verified by a positive double-antibody sandwich-ELISA (Agden Ltd., Ayr, Scotland). The tuber lesions had an absorbance value (405 nm) at least two times greater than that of the negative control sample, which consisted of a healthy tuber. Total RNA was extracted from lesions of six different tubers that tested positive by ELISA using a Total RNA Isolation kit (Promega Corp. Madison, WI). These extracts were tested for PMTV by reverse transcription (RT)-PCR using two different sets of primers. The primer set H360/C819 targeted the coat protein (CP) of PMTV and yielded an amplicon of 460 bp (4). The amplicons generated from the necrotic lesions were cloned (TOPO Cloning; Invitrogen, Carlsbad, CA) and sequenced. Another set of primers, pmtF4/pmtR4, designed to bind to a region in RNA 2 of PMTV, yielded a 417-bp amplicon that also was cloned and sequenced (3). The sequences from all six tuber lesions were identical for the respective primer sets. A consensus sequence for each primer pair was submitted to GenBank (Accession No. HM776171 for primers pmtF4/pmtR4 and No. HM776172 for primers H360/C819). The sequences obtained from the H360/C819 and pmtF4/pmtR4 amplicons were 99% identical to the corresponding regions of PMTV isolates from Northern Europe (GenBank Accession Nos. AM503629 and AJ277556, respectively). Freeze-dried, necrotic tuber tissue from all six tubers was also tested at a USDA Laboratory in Prosser, WA by RT-PCR with the H360/C819 primer pair (4), confirming the results above. Cloning and sequencing of one of the amplicons revealed 100% similarity to the sequence described above for these primers (GenBank Accession No. HM776172), confirming the presence of PMTV in the symptomatic tubers. None of the symptomatic tubers tested positive for Tobacco rattle virus, Tomato spotted wilt virus, Alfalfa mosaic virus, Potato leafroll virus, or the necrotic strains of Potato virus Y by RT-PCR. To our knowledge this is the first report of PMTV in North Dakota. References: (1) R. A. C. Jones and B. D. Harrsion. Ann. Appl. Biol. 63:1, 1969. (2) D. H. Lambert et al. Plant Dis. 87:872, 2003. (3) J. Santala et al. Ann. Appl. Biol. Online publication. DOI: 10.1111/j.1744-7348.2010.00423.x (4) H. Xu et al. Plant Dis. 88:363, 2004.
Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, ...and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.
Response to Li and Hopper Thomas, Minta; Sakoda, Lori C; Hoffmeister, Michael ...
American journal of human genetics,
03/2021, Letnik:
108, Številka:
3
Journal Article
This is the first report of stunting, stem distortion, delayed emergence and foliar TRV symptoms on potato in the Pacific Northwest where approximately 50% of the US potato crop is grown. The shift ...in use from 1,3 dichloropropene to oxamyl may suggest these symptoms will be more frequently observed in the future.
Accepted for publication 19 May 2007. Published 17 September 2007.
These facets of worker displacement are investigated - definition, detection and consequence. A definition of displacement is sought that permits the identification of those who are truly at risk of ...adverse consequences because of this event. The detection goal is to indentify data elements in available administrative data sources that can be used for this purpose. A consolidated database is used that represents three states in the US and seven industry sectors, which includes seven years of quarterly employer/industry affliation and earnings pairings. Estimated earnings losses are shown to be sensitive to the definition of displacement that is adopted. Available data elements do not support the reliable prediction of adverse consequences associated with displacement relative to earnings discontinuities that accompany other causal definitations of unemployment.
SIMULTANEOUS EQUATION ESTIMATES OF JOB SEARCH DURATION RELATIONSHIPS PROVIDE A MORE ACCURATE REPRESENTATION OF THE REEMPLOYMENT PROCESS THAN DO SINGLE EQUATION ANALYSES. GIVEN A CONSTANT WAGE OFFER ...DISTRIBUTION AND A DECLINING ASKING WAGE OVER TIME, THE PROBABILITY OF RECEIVING AN OFFER AT LEAST EQUAL TO THE ASKING WAGE INCREASES WITH UNEMPLOYMENT DURATION. PREVIOUS ANALYSES HAVE IMPLICITLY ASSUMED DURATION OF UNEMPLOYMENT TO BE INDEPENDENT OF THE LEVEL OF THE ASKING WAGE BY USING SINGLE EQUATION ESTIMATION TECHNIQUES SUCH AS ORDINARY LEAST SQUARES (OLS) TO ESTIMATE THE ASKING WAGE DURATION RELATION. SIMULTANEOUS EQUATION ESTIMATES IMPLY AN AVERAGE MONTHLY DECLINE IN ASKING WAGES OF 5.55 PERCENT FOR UNEMPLOYED INDIVIDUALS RECEIVING LESS THAN THE MAXIMUM WEEKLY BENEFIT AMOUNT AND 3.03 PERCENT FOR THOSE RECEIVING THE MAXIMUM. THESE ESTIMATES ARE CONSIDERABLY LARGER THAN THOSE OBTAINED UTILIZING OLS TECHNIQUES. EQUATIONS. REFERENCES.
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