rai Nearby Lightning Shut Down a Woman's Brain Implant By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Nearby Lightning Shut Down a Woman's Brain ImplantCategory: Health NewsCreated: 5/1/2018 12:00:00 AMLast Editorial Review: 5/1/2018 12:00:00 AM Full Article
rai Further Signs That Too Much Sitting Can Raise Clot Risk By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Further Signs That Too Much Sitting Can Raise Clot RiskCategory: Health NewsCreated: 5/3/2018 12:00:00 AMLast Editorial Review: 5/4/2018 12:00:00 AM Full Article
rai The Cold Truth About Migraine Headaches By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: The Cold Truth About Migraine HeadachesCategory: Health NewsCreated: 5/3/2018 12:00:00 AMLast Editorial Review: 5/4/2018 12:00:00 AM Full Article
rai Breast Milk Has Biggest Benefit for Preemies' Brains: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Breast Milk Has Biggest Benefit for Preemies' Brains: StudyCategory: Health NewsCreated: 4/27/2019 12:00:00 AMLast Editorial Review: 4/29/2019 12:00:00 AM Full Article
rai Morning Exercise Kick-Starts Seniors' Brains By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Morning Exercise Kick-Starts Seniors' BrainsCategory: Health NewsCreated: 5/2/2019 12:00:00 AMLast Editorial Review: 5/2/2019 12:00:00 AM Full Article
rai Could Alzheimer's Spread Like an Infection Throughout the Brain? By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Could Alzheimer's Spread Like an Infection Throughout the Brain?Category: Health NewsCreated: 5/1/2019 12:00:00 AMLast Editorial Review: 5/2/2019 12:00:00 AM Full Article
rai Job Strain May Boost Odds of Serious Artery Disease By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Job Strain May Boost Odds of Serious Artery DiseaseCategory: Health NewsCreated: 4/28/2020 12:00:00 AMLast Editorial Review: 4/28/2020 12:00:00 AM Full Article
rai Love in the Time of Coronavirus: Couples Feel the Strain of Lockdown By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Love in the Time of Coronavirus: Couples Feel the Strain of LockdownCategory: Health NewsCreated: 4/28/2020 12:00:00 AMLast Editorial Review: 4/29/2020 12:00:00 AM Full Article
rai Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk? By www.medicinenet.com Published On :: Wed, 25 Mar 2020 00:00:00 PDT Title: Could Cellphone, Microwave Radiation During Pregnancy Raise ADHD Risk?Category: Health NewsCreated: 3/24/2020 12:00:00 AMLast Editorial Review: 3/25/2020 12:00:00 AM Full Article
rai Pregnancy Complications Raise Future Odds of Preterm Birth: Study By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: Pregnancy Complications Raise Future Odds of Preterm Birth: StudyCategory: Health NewsCreated: 5/1/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
rai Sometimes, Aspirin May Be Enough to Ease Migraines By www.medicinenet.com Published On :: Tue, 10 Dec 2019 00:00:00 PDT Title: Sometimes, Aspirin May Be Enough to Ease MigrainesCategory: Health NewsCreated: 12/10/2019 12:00:00 AMLast Editorial Review: 12/10/2019 12:00:00 AM Full Article
rai FDA Approves New Type of Drug to Treat Migraines By www.medicinenet.com Published On :: Tue, 24 Dec 2019 00:00:00 PDT Title: FDA Approves New Type of Drug to Treat MigrainesCategory: Health NewsCreated: 12/23/2019 12:00:00 AMLast Editorial Review: 12/24/2019 12:00:00 AM Full Article
rai Sleep Disturbances May Trigger Migraine By www.medicinenet.com Published On :: Fri, 27 Dec 2019 00:00:00 PDT Title: Sleep Disturbances May Trigger MigraineCategory: Health NewsCreated: 12/26/2019 12:00:00 AMLast Editorial Review: 12/27/2019 12:00:00 AM Full Article
rai Could Smartphones Be Making Migraines Even Tougher to Treat? By www.medicinenet.com Published On :: Thu, 5 Mar 2020 00:00:00 PDT Title: Could Smartphones Be Making Migraines Even Tougher to Treat?Category: Health NewsCreated: 3/4/2020 12:00:00 AMLast Editorial Review: 3/5/2020 12:00:00 AM Full Article
rai 10 New Weapons in the War on Migraines By www.medicinenet.com Published On :: Wed, 11 Mar 2020 00:00:00 PDT Title: 10 New Weapons in the War on MigrainesCategory: Health NewsCreated: 3/10/2020 12:00:00 AMLast Editorial Review: 3/11/2020 12:00:00 AM Full Article
rai Trial Finds Acupuncture May Help Prevent Migraines By www.medicinenet.com Published On :: Fri, 27 Mar 2020 00:00:00 PDT Title: Trial Finds Acupuncture May Help Prevent MigrainesCategory: Health NewsCreated: 3/26/2020 12:00:00 AMLast Editorial Review: 3/27/2020 12:00:00 AM Full Article
rai Gentle Yoga May Deliver Migraine Relief By www.medicinenet.com Published On :: Thu, 7 May 2020 00:00:00 PDT Title: Gentle Yoga May Deliver Migraine ReliefCategory: Health NewsCreated: 5/6/2020 12:00:00 AMLast Editorial Review: 5/7/2020 12:00:00 AM Full Article
rai Key Areas of the Brain Triggered in Recent Heart Attack Survivors By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Key Areas of the Brain Triggered in Recent Heart Attack SurvivorsCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
rai Heavy Drinking Tied to Raised Stroke Risk, Study Finds By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: Heavy Drinking Tied to Raised Stroke Risk, Study FindsCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
rai Experts Cast Doubt on Notion That New Strain of Coronavirus Is More Infectious By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Experts Cast Doubt on Notion That New Strain of Coronavirus Is More InfectiousCategory: Health NewsCreated: 5/7/2020 12:00:00 AMLast Editorial Review: 5/8/2020 12:00:00 AM Full Article
rai Gentle Yoga May Deliver Migraine Relief By www.webmd.com Published On :: Thu, 07 May 2020 10:33:28 EST People suffering from regular migraines despite medication might consider investing in a yoga mat. Full Article
rai What Day Is It? This Is Your Brain on Quarantine By www.webmd.com Published On :: Thu, 07 May 2020 17:06:59 EST If it feels like all your internal clocks are melting as your stay-at-home days drone on, you are not alone. Researchers say that people in various levels of COVID-19 quarantine around the world are reporting a distorted sense of time. Full Article
rai Sprains and Strains By www.medicinenet.com Published On :: Fri, 10 Apr 2020 00:00:00 PDT Title: Sprains and StrainsCategory: Diseases and ConditionsCreated: 3/5/2003 12:00:00 AMLast Editorial Review: 4/10/2020 12:00:00 AM Full Article
rai Study Ties Brain Inflammation to Several Types of Dementia By www.medicinenet.com Published On :: Wed, 18 Mar 2020 00:00:00 PDT Title: Study Ties Brain Inflammation to Several Types of DementiaCategory: Health NewsCreated: 3/18/2020 12:00:00 AMLast Editorial Review: 3/18/2020 12:00:00 AM Full Article
rai Dirty Air Might Raise Your Odds for Dementia By www.medicinenet.com Published On :: Wed, 1 Apr 2020 00:00:00 PDT Title: Dirty Air Might Raise Your Odds for DementiaCategory: Health NewsCreated: 3/31/2020 12:00:00 AMLast Editorial Review: 4/1/2020 12:00:00 AM Full Article
rai Brain Plaques Signal Alzheimer's Even Before Other Symptoms Emerge: Study By www.medicinenet.com Published On :: Tue, 14 Apr 2020 00:00:00 PDT Title: Brain Plaques Signal Alzheimer's Even Before Other Symptoms Emerge: StudyCategory: Health NewsCreated: 4/13/2020 12:00:00 AMLast Editorial Review: 4/14/2020 12:00:00 AM Full Article
rai Potato & Sausages, Cold Cuts a Bad Combo for Your Brain By www.medicinenet.com Published On :: Thu, 23 Apr 2020 00:00:00 PDT Title: Potato & Sausages, Cold Cuts a Bad Combo for Your BrainCategory: Health NewsCreated: 4/22/2020 12:00:00 AMLast Editorial Review: 4/23/2020 12:00:00 AM Full Article
rai Rheumatoid Arthritis, Low Folate Levels Raise Heart Risks By www.medicinenet.com Published On :: Tue, 3 Mar 2020 00:00:00 PDT Title: Rheumatoid Arthritis, Low Folate Levels Raise Heart RisksCategory: Health NewsCreated: 3/2/2020 12:00:00 AMLast Editorial Review: 3/3/2020 12:00:00 AM Full Article
rai Injuries a Drain on Employee Productivity By www.medicinenet.com Published On :: Tue, 5 May 2020 00:00:00 PDT Title: Injuries a Drain on Employee ProductivityCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/5/2020 12:00:00 AM Full Article
rai Blood Pressure Spikes at Night May Spell Trouble for Brain By www.medicinenet.com Published On :: Mon, 20 Apr 2020 00:00:00 PDT Title: Blood Pressure Spikes at Night May Spell Trouble for BrainCategory: Health NewsCreated: 4/17/2020 12:00:00 AMLast Editorial Review: 4/20/2020 12:00:00 AM Full Article
rai AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older People By www.medicinenet.com Published On :: Tue, 31 Mar 2020 00:00:00 PDT Title: AHA News: Dropping Blood Pressure May Predict Frailty, Falls in Older PeopleCategory: Health NewsCreated: 3/30/2020 12:00:00 AMLast Editorial Review: 3/31/2020 12:00:00 AM Full Article
rai Long Periods in Space Alter Astronauts' Brains By www.medicinenet.com Published On :: Wed, 15 Apr 2020 00:00:00 PDT Title: Long Periods in Space Alter Astronauts' BrainsCategory: Health NewsCreated: 4/14/2020 12:00:00 AMLast Editorial Review: 4/15/2020 12:00:00 AM Full Article
rai Greenhouse Gases Bad for Your Brain By www.medicinenet.com Published On :: Fri, 24 Apr 2020 00:00:00 PDT Title: Greenhouse Gases Bad for Your BrainCategory: Health NewsCreated: 4/23/2020 12:00:00 AMLast Editorial Review: 4/24/2020 12:00:00 AM Full Article
rai Some NFL Players May Be Misdiagnosed With Brain Disease: Study By www.medicinenet.com Published On :: Tue, 28 Apr 2020 00:00:00 PDT Title: Some NFL Players May Be Misdiagnosed With Brain Disease: StudyCategory: Health NewsCreated: 4/27/2020 12:00:00 AMLast Editorial Review: 4/28/2020 12:00:00 AM Full Article
rai Magnetic Brain 'Zap' Shows Promise Against Severe Depression By www.medicinenet.com Published On :: Wed, 8 Apr 2020 00:00:00 PDT Title: Magnetic Brain 'Zap' Shows Promise Against Severe DepressionCategory: Health NewsCreated: 4/7/2020 12:00:00 AMLast Editorial Review: 4/8/2020 12:00:00 AM Full Article
rai Could AI Help Doctors Map Out Treatments for Brain Cancers? By www.medicinenet.com Published On :: Mon, 27 Apr 2020 00:00:00 PDT Title: Could AI Help Doctors Map Out Treatments for Brain Cancers?Category: Health NewsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/27/2020 12:00:00 AM Full Article
rai First Good Evidence That Brain Hits 'Replay' While You Sleep By www.medicinenet.com Published On :: Wed, 6 May 2020 00:00:00 PDT Title: First Good Evidence That Brain Hits 'Replay' While You SleepCategory: Health NewsCreated: 5/5/2020 12:00:00 AMLast Editorial Review: 5/6/2020 12:00:00 AM Full Article
rai Inhibition of Importin {beta}1 Augments the Anticancer Effect of Agonistic Anti-Death Receptor 5 Antibody in TRAIL-resistant Tumor Cells By mct.aacrjournals.org Published On :: 2020-05-04T05:39:42-07:00 TNF-related apoptosis-inducing ligand (TRAIL) and an agonistic antibody against the death-inducing TRAIL receptor 5, DR5, are thought to selectively induce tumor cell death and therefore, have gained attention as potential therapeutics currently under investigation in several clinical trials. However, some tumor cells are resistant to TRAIL/DR5–induced cell death, even though they express DR5. Previously, we reported that DR5 is transported into the nucleus by importin β1, and knockdown of importin β1 upregulates cell surface expression of DR5 resulting in increased TRAIL sensitivity in vitro. Here, we examined the impact of importin β1 knockdown on agonistic anti-human DR5 (hDR5) antibody therapy. Drug-inducible importin β1 knockdown sensitizes HeLa cells to TRAIL-induced cell death in vitro, and exerts an antitumor effect when combined with agonistic anti-hDR5 antibody administration in vivo. Therapeutic importin β1 knockdown, administered via the atelocollagen delivery system, as well as treatment with the importin β inhibitor, importazole, induced regression and/or eradication of two human TRAIL-resistant tumor cells when combined with agonistic anti-hDR5 antibody treatment. Thus, these findings suggest that the inhibition of importin β1 would be useful to improve the therapeutic effects of agonistic anti-hDR5 antibody against TRAIL-resistant cancers. Full Article
rai Redefining Medical Competencies for an Oral Medicine Specialty Training Curriculum Using a Modified Delphi Technique By www.jdentaled.org Published On :: 2019-12-01T06:00:19-08:00 This article describes the development of medical competencies for oral medicine specialty training in the UK and Ireland by a collaborative working group using a modified Delphi technique. The current specialty training curriculum for oral medicine (OM) in the UK was developed by a working group including members of the British Society for Oral Medicine (BSOM) and members of the Specialty Advisory Committee for Additional Dental Specialties (SACADS) and adopted by the UK General Dental Council (GDC) in 2010. When the curriculum was developed, the entry requirements for specialty training in OM included undergraduate degrees in both dentistry and medicine. At the time of adoption, the requirement for a medical degree was removed. Medical competencies were assumed to have been delivered in medical undergraduate and postgraduate training. Accordingly, there was a need to define the medical competencies for OM specialty training to benefit trainees, trainers, and assessors. In 2018, a group comprising specialty trainers, recent former specialty trainees, and current specialty trainees in OM held face-to-face meetings in addition to email discussions and developed an updated curriculum document to better reflect the medical competencies required in specialty training. A collaborative modified Delphi approach was used to evaluate medical foundation competencies and to include only those that were considered relevant to OM specialty training. A list of relevant and achievable medical competencies was determined that has been approved by SACADS and will be incorporated into a revised OM curriculum from the UK GDC. The newly agreed-upon document for medical competencies in OM specialty training will serve as a reference for trainees, trainers, and assessors and reflects a successful use of a modified Delphi approach. Full Article
rai Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains By mbio.asm.org Published On :: 2020-03-03T01:30:27-08:00 ABSTRACT Obesity is associated with increased disease severity, elevated viral titers in exhaled breath, and significantly prolonged viral shed during influenza A virus infection. Due to the mutable nature of RNA viruses, we questioned whether obesity could also influence influenza virus population diversity. Here, we show that minor variants rapidly emerge in obese mice. The variants exhibit increased viral replication, resulting in enhanced virulence in wild-type mice. The increased diversity of the viral population correlated with decreased type I interferon responses, and treatment of obese mice with recombinant interferon reduced viral diversity, suggesting that the delayed antiviral response exhibited in obesity permits the emergence of a more virulent influenza virus population. This is not unique to obese mice. Obesity-derived normal human bronchial epithelial (NHBE) cells also showed decreased interferon responses and increased viral replication, suggesting that viral diversity also was impacted in this increasing population. IMPORTANCE Currently, 50% of the adult population worldwide is overweight or obese. In these studies, we demonstrate that obesity not only enhances the severity of influenza infection but also impacts viral diversity. The altered microenvironment associated with obesity supports a more diverse viral quasispecies and affords the emergence of potentially pathogenic variants capable of inducing greater disease severity in lean hosts. This is likely due to the impaired interferon response, which is seen in both obese mice and obesity-derived human bronchial epithelial cells, suggesting that obesity, aside from its impact on influenza virus pathogenesis, permits the stochastic accumulation of potentially pathogenic viral variants, raising concerns about its public health impact as the prevalence of obesity continues to rise. Full Article
rai Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection By mbio.asm.org Published On :: 2020-04-07T01:31:16-07:00 ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection. IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19. Full Article
rai A large Taenidium burrow from the Upper Carboniferous of Corrie, Isle of Arran, and remarks on the association of Taenidium burrows and Diplichnites trails By sjg.lyellcollection.org Published On :: 2019-11-29T02:21:48-08:00 Large un-walled backfilled burrows of the Taenidium type are known from Paleozoic deltaic marine environments worldwide where they are often associated with Diplichnites trackways. The latter are generally attributed to arthropleurid myriapods and it may be that the burrows were also made by these animals. Here we describe a Taenidium burrow from the Limestone Coal Formation of the Isle of Arran, a formation that also hosts a well-known example of Diplichnites, supporting the association of the two types of trace fossil and extending their known co-occurrence upward into the Upper Carboniferous. Full Article
rai Hot on the Trail of DREB2A Protein Stability By www.plantphysiol.org Published On :: 2020-05-08T08:30:48-07:00 Full Article
rai The Time Is Now: Standardized Sedation Training for Pediatric Hospitalists By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 Full Article
rai Genetic Associations in Four Decades of Multienvironment Trials Reveal Agronomic Trait Evolution in Common Bean [Genetics of Complex Traits] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Multienvironment trials (METs) are widely used to assess the performance of promising crop germplasm. Though seldom designed to elucidate genetic mechanisms, MET data sets are often much larger than could be duplicated for genetic research and, given proper interpretation, may offer valuable insights into the genetics of adaptation across time and space. The Cooperative Dry Bean Nursery (CDBN) is a MET for common bean (Phaseolus vulgaris) grown for > 70 years in the United States and Canada, consisting of 20–50 entries each year at 10–20 locations. The CDBN provides a rich source of phenotypic data across entries, years, and locations that is amenable to genetic analysis. To study stable genetic effects segregating in this MET, we conducted genome-wide association studies (GWAS) using best linear unbiased predictions derived across years and locations for 21 CDBN phenotypes and genotypic data (1.2 million SNPs) for 327 CDBN genotypes. The value of this approach was confirmed by the discovery of three candidate genes and genomic regions previously identified in balanced GWAS. Multivariate adaptive shrinkage (mash) analysis, which increased our power to detect significant correlated effects, found significant effects for all phenotypes. Mash found two large genomic regions with effects on multiple phenotypes, supporting a hypothesis of pleiotropic or linked effects that were likely selected on in pursuit of a crop ideotype. Overall, our results demonstrate that statistical genomics approaches can be used on MET phenotypic data to discover significant genetic effects and to define genomic regions associated with crop improvement. Full Article
rai Pathogen Genetic Control of Transcriptome Variation in the Arabidopsis thaliana - Botrytis cinerea Pathosystem [Genetics of Complex Traits] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 In plant–pathogen relations, disease symptoms arise from the interaction of the host and pathogen genomes. Host–pathogen functional gene interactions are well described, whereas little is known about how the pathogen genetic variation modulates both organisms’ transcriptomes. To model and generate hypotheses on a generalist pathogen control of gene expression regulation, we used the Arabidopsis thaliana–Botrytis cinerea pathosystem and the genetic diversity of a collection of 96 B. cinerea isolates. We performed expression-based genome-wide association (eGWA) for each of 23,947 measurable transcripts in Arabidopsis (host), and 9267 measurable transcripts in B. cinerea (pathogen). Unlike other eGWA studies, we detected a relative absence of locally acting expression quantitative trait loci (cis-eQTL), partly caused by structural variants and allelic heterogeneity hindering their identification. This study identified several distantly acting trans-eQTL linked to eQTL hotspots dispersed across Botrytis genome that altered only Botrytis transcripts, only Arabidopsis transcripts, or transcripts from both species. Gene membership in the trans-eQTL hotspots suggests links between gene expression regulation and both known and novel virulence mechanisms in this pathosystem. Genes annotated to these hotspots provide potential targets for blocking manipulation of the host response by this ubiquitous generalist necrotrophic pathogen. Full Article
rai A Novel Variation in the FRIZZLE PANICLE (FZP) Gene Promoter Improves Grain Number and Yield in Rice [Genetics of Complex Traits] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Secondary branch number per panicle plays a crucial role in regulating grain number and yield in rice. Here, we report the positional cloning and functional characterization for SECONDARY BRANCH NUMBER7 (qSBN7), a quantitative trait locus affecting secondary branch per panicle and grain number. Our research revealed that the causative variants of qSBN7 are located in the distal promoter region of FRIZZLE PANICLE (FZP), a gene previously associated with the repression of axillary meristem development in rice spikelets. qSBN7 is a novel allele of FZP that causes an ~56% decrease in its transcriptional level, leading to increased secondary branch and grain number, and reduced grain length. Field evaluations showed that qSBN7 increased grain yield by 10.9% in a temperate japonica variety, TN13, likely due to its positive effect on sink capacity. Our findings suggest that incorporation of qSBN7 can increase yield potential and improve the breeding of elite rice varieties. Full Article
rai Deciphering Sex-Specific Genetic Architectures Using Local Bayesian Regressions [Genetics of Complex Traits] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Many complex human traits exhibit differences between sexes. While numerous factors likely contribute to this phenomenon, growing evidence from genome-wide studies suggest a partial explanation: that males and females from the same population possess differing genetic architectures. Despite this, mapping gene-by-sex (GxS) interactions remains a challenge likely because the magnitude of such an interaction is typically and exceedingly small; traditional genome-wide association techniques may be underpowered to detect such events, due partly to the burden of multiple test correction. Here, we developed a local Bayesian regression (LBR) method to estimate sex-specific SNP marker effects after fully accounting for local linkage-disequilibrium (LD) patterns. This enabled us to infer sex-specific effects and GxS interactions either at the single SNP level, or by aggregating the effects of multiple SNPs to make inferences at the level of small LD-based regions. Using simulations in which there was imperfect LD between SNPs and causal variants, we showed that aggregating sex-specific marker effects with LBR provides improved power and resolution to detect GxS interactions over traditional single-SNP-based tests. When using LBR to analyze traits from the UK Biobank, we detected a relatively large GxS interaction impacting bone mineral density within ABO, and replicated many previously detected large-magnitude GxS interactions impacting waist-to-hip ratio. We also discovered many new GxS interactions impacting such traits as height and body mass index (BMI) within regions of the genome where both male- and female-specific effects explain a small proportion of phenotypic variance (R2 < 1 x 10–4), but are enriched in known expression quantitative trait loci. Full Article
rai Dominance Effects and Functional Enrichments Improve Prediction of Agronomic Traits in Hybrid Maize [Genomic Prediction] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Single-cross hybrids have been critical to the improvement of maize (Zea mays L.), but the characterization of their genetic architectures remains challenging. Previous studies of hybrid maize have shown the contribution of within-locus complementation effects (dominance) and their differential importance across functional classes of loci. However, they have generally considered panels of limited genetic diversity, and have shown little benefit from genomic prediction based on dominance or functional enrichments. This study investigates the relevance of dominance and functional classes of variants in genomic models for agronomic traits in diverse populations of hybrid maize. We based our analyses on a diverse panel of inbred lines crossed with two testers representative of the major heterotic groups in the U.S. (1106 hybrids), as well as a collection of 24 biparental populations crossed with a single tester (1640 hybrids). We investigated three agronomic traits: days to silking (DTS), plant height (PH), and grain yield (GY). Our results point to the presence of dominance for all traits, but also among-locus complementation (epistasis) for DTS and genotype-by-environment interactions for GY. Consistently, dominance improved genomic prediction for PH only. In addition, we assessed enrichment of genetic effects in classes defined by genic regions (gene annotation), structural features (recombination rate and chromatin openness), and evolutionary features (minor allele frequency and evolutionary constraint). We found support for enrichment in genic regions and subsequent improvement of genomic prediction for all traits. Our results suggest that dominance and gene annotations improve genomic prediction across diverse populations in hybrid maize. Full Article
rai Fast Algorithms for Conducting Large-Scale GWAS of Age-at-Onset Traits Using Cox Mixed-Effects Models [Statistical Genetics and Genomics] By www.genetics.org Published On :: 2020-05-05T06:43:41-07:00 Age-at-onset is one of the critical traits in cohort studies of age-related diseases. Large-scale genome-wide association studies (GWAS) of age-at-onset traits can provide more insights into genetic effects on disease progression and transitions between stages. Moreover, proportional hazards (or Cox) regression models can achieve higher statistical power in a cohort study than a case-control trait using logistic regression. Although mixed-effects models are widely used in GWAS to correct for sample dependence, application of Cox mixed-effects models (CMEMs) to large-scale GWAS is so far hindered by intractable computational cost. In this work, we propose COXMEG, an efficient R package for conducting GWAS of age-at-onset traits using CMEMs. COXMEG introduces fast estimation algorithms for general sparse relatedness matrices including, but not limited to, block-diagonal pedigree-based matrices. COXMEG also introduces a fast and powerful score test for dense relatedness matrices, accounting for both population stratification and family structure. In addition, COXMEG generalizes existing algorithms to support positive semidefinite relatedness matrices, which are common in twin and family studies. Our simulation studies suggest that COXMEG, depending on the structure of the relatedness matrix, is orders of magnitude computationally more efficient than coxme and coxph with frailty for GWAS. We found that using sparse approximation of relatedness matrices yielded highly comparable results in controlling false-positive rate and retaining statistical power for an ethnically homogeneous family-based sample. By applying COXMEG to a study of Alzheimer’s disease (AD) with a Late-Onset Alzheimer’s Disease Family Study from the National Institute on Aging sample comprising 3456 non-Hispanic whites and 287 African Americans, we identified the APOE 4 variant with strong statistical power (P = 1e–101), far more significant than that reported in a previous study using a transformed variable and a marginal Cox model. Furthermore, we identified novel SNP rs36051450 (P = 2e–9) near GRAMD1B, the minor allele of which significantly reduced the hazards of AD in both genders. These results demonstrated that COXMEG greatly facilitates the application of CMEMs in GWAS of age-at-onset traits. Full Article