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https://www.readbyqxmd.com/read/28238358/integrating-gene-expression-with-summary-association-statistics-to-identify-genes-associated-with-30-complex-traits
#1
Nicholas Mancuso, Huwenbo Shi, Pagé Goddard, Gleb Kichaev, Alexander Gusev, Bogdan Pasaniuc
Although genome-wide association studies (GWASs) have identified thousands of risk loci for many complex traits and diseases, the causal variants and genes at these loci remain largely unknown. Here, we introduce a method for estimating the local genetic correlation between gene expression and a complex trait and utilize it to estimate the genetic correlation due to predicted expression between pairs of traits. We integrated gene expression measurements from 45 expression panels with summary GWAS data to perform 30 multi-tissue transcriptome-wide association studies (TWASs)...
February 17, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28235564/candidate-novel-long-noncoding-rnas-micrornas-and-putative-drugs-for-parkinson-s-disease-using-a-robust-and-efficient-genome-wide-association-study
#2
Zahra Mortezaei, Hossein Lanjanian, Ali Masoudi-Nejad
Parkinson's disease (PD) is a neurodegenerative disorder with serious symptoms of which, are not clearly demonstrated at the beginning stages of the disease, making treatment challenging. Understanding the genetic causes of PD can be useful for determining its mechanisms and proposing treatments and preventive methods. For different populations with different genetic backgrounds and lifestyles, genome-wide association studies (GWASs) represent a crucial approach for genetic analysis. In this study, a robust and efficient GWAS without dimensionality reduction applied to evaluate heritability and genetic causes of PD in the German and US populations...
February 21, 2017: Genomics
https://www.readbyqxmd.com/read/28231077/association-of-genetic-variation-in-the-tachykinin-receptor-3-locus-with-hot-flashes-and-night-sweats-in-the-women-s-health-initiative-study
#3
Carolyn J Crandall, JoAnn E Manson, Chancellor Hohensee, Steve Horvath, Jean Wactawski-Wende, Erin S LeBlanc, Mara Z Vitolins, Rami Nassir, Janet S Sinsheimer
OBJECTIVE: Vasomotor symptoms (VMS, ie, hot flashes or night sweats) are reported by many, but not all, women. The extent to which VMS are genetically determined is unknown. We evaluated the relationship of genetic variation and VMS. METHODS: In this observational study, we accessed data from three genome-wide association studies (GWAS) (SNP Health Association Resource cohort [SHARe], WHI Memory Study cohort [WHIMS+], and Genome-Wide Association Studies of Treatment Response in Randomized Clinical Trials [GARNET] studies, total n = 17,695) of European American, African American, and Hispanic American postmenopausal women aged 50 to 79 years at baseline in the Women's Health Initiative Study...
March 2017: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/28229505/a-variant-in-a-cis-regulatory-element-enhances-claudin-14-expression-and-is-associated-with-pediatric-onset-hypercalciuria-and-kidney-stones
#4
Megan E Ure, Emma Heydari, Wanling Pan, Ajay Ramesh, Sabah Rehman, Catherine Morgan, Maury Pinsk, Robin Erickson, Johannes M Herrmann, Henrik Dimke, Emmanuelle Cordat, Mathieu Lemaire, Michael Walter, R Todd Alexander
The greatest risk factor for kidney stones is hypercalciuria, the etiology of which is largely unknown. A recent genome-wide association study (GWAS) linked hypercalciuria and kidney stones to a claudin-14 (CLDN14) risk haplotype. However, the underlying molecular mechanism was not delineated. Recently, renal CLDN14 expression was found to increase in response to increased plasma calcium, thereby inducing calciuria. We hypothesized therefore that some children with hypercalciuria and kidney stones harbor a CLDN14 variant that inappropriately increases gene expression...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28228184/a-novel-approach-for-pathway-analysis-of-gwas-data-highlights-role-of-bmp-signaling-and-muscle-cell-differentiation-in-colorectal-cancer-susceptibility-erratum
#5
Aniket Mishra, Stuart MacGregor
The publishers regret to announce that the affiliation for the above paper was incorrectly inserted. The correct affiliation is below: Aniket Mishra1, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colorectal Cancer Family Registry (CCFR), and Stuart MacGregor1 1 Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
February 23, 2017: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://www.readbyqxmd.com/read/28228157/genetics-and-genomics-of-dilated-cardiomyopathy-and-systolic-heart-failure
#6
REVIEW
Upasana Tayal, Sanjay Prasad, Stuart A Cook
Heart failure is a major health burden, affecting 40 million people globally. One of the main causes of systolic heart failure is dilated cardiomyopathy (DCM), the leading global indication for heart transplantation. Our understanding of the genetic basis of both DCM and systolic heart failure has improved in recent years with the application of next-generation sequencing and genome-wide association studies (GWAS). This has enabled rapid sequencing at scale, leading to the discovery of many novel rare variants in DCM and of common variants in both systolic heart failure and DCM...
February 22, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28224735/genetic-risk-variants-for-social-anxiety
#7
Murray B Stein, Chia-Yen Chen, Sonia Jain, Kevin P Jensen, Feng He, Steven G Heeringa, Ronald C Kessler, Adam Maihofer, Matthew K Nock, Stephan Ripke, Xiaoying Sun, Michael L Thomas, Robert J Ursano, Jordan W Smoller, Joel Gelernter
Social anxiety is a neurobehavioral trait characterized by fear and reticence in social situations. Twin studies have shown that social anxiety has a heritable basis, shared with neuroticism and extraversion, but genetic studies have yet to demonstrate robust risk variants. We conducted genomewide association analysis (GWAS) of subjects within the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS) to (i) determine SNP-based heritability of social anxiety; (ii) discern genetic risk loci for social anxiety; and (iii) determine shared genetic risk with neuroticism and extraversion...
March 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28223988/the-impact-of-genotyping-by-sequencing-pipelines-on-snp-discovery-and-identification-of-markers-associated-with-verticillium-wilt-resistance-in-autotetraploid-alfalfa-medicago-sativa-l
#8
Long-Xi Yu, Ping Zheng, Suresh Bhamidimarri, Xiang-Ping Liu, Dorie Main
Verticillium wilt (VW) of alfalfa is a soilborne disease causing severe yield loss in alfalfa. To identify molecular markers associated with VW resistance, we used an integrated framework of genome-wide association study (GWAS) with high-throughput genotyping by sequencing (GBS) to identify loci associated with VW resistance in an F1 full-sib alfalfa population. Phenotyping was performed using manual inoculation of the pathogen to cloned plants of each individual and disease severity was scored using a standard scale...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28223964/mouse-models-of-human-gwas-hits-for-obesity-and-diabetes-in-the-post-genomic-era-time-for-reevaluation
#9
Samantha Laber, Roger D Cox
No abstract text is available yet for this article.
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28222097/a-genome-wide-association-study-identifies-a-lncrna-as-risk-factor-for-pathological-inflammatory-responses-in-leprosy
#10
Vinicius M Fava, Jeremy Manry, Aurélie Cobat, Marianna Orlova, Nguyen Van Thuc, Milton O Moraes, Carolinne Sales-Marques, Mariane M A Stefani, Ana Carla P Latini, Andrea F Belone, Vu Hong Thai, Laurent Abel, Alexandre Alcaïs, Erwin Schurr
Leprosy Type-1 Reactions (T1Rs) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage. Here, we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R. We discovered, replicated and validated T1R-specific associations with SNPs located in chromosome region 10p21.2. Combined analysis across the three independent samples resulted in strong evidence of association of rs1875147 with T1R (p = 4...
February 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28220687/environmental-factors-seven-gwas-identified-susceptibility-loci-and-risk-of-gastric-cancer-and-its-precursors-in-a-chinese-population
#11
Meng Cai, Shuyang Dai, Wanqing Chen, Changfa Xia, Lingeng Lu, Shuguang Dai, Jun Qi, Minjie Wang, Meilin Wang, Lanping Zhou, Fuhua Lei, Tingting Zuo, Hongmei Zeng, Xiaohang Zhao
Gene-environment interactions may increase gastric cancer (GC) risk. Seven susceptibility loci identified by genome-wide association studies (GWASs) suggest that genetic factors play a role in gastric carcinogenesis. Meanwhile, Helicobacter pylori (H. pylori) infection, smoking, and alcohol drinking are also important environmental factors for gastric cancer. However, studies to explore the role of gene-environment interactions in gastric carcinogenesis, and particularly the relationship between the seven susceptibility loci and their potential interactions with H...
February 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28218981/the-genetic-architecture-of-amino-acids-dissection-by-association-and-linkage-analysis-in-maize
#12
Min Deng, Dongqin Li, Jingyun Luo, Yingjie Xiao, Haijun Liu, Qingchun Pan, Xuehai Zhang, Minliang Jin, Mingchao Zhao, Jianbing Yan
Amino acids are both constituents of proteins, providing the essential nutrition for humans and animals, and signaling molecules regulating the growth and development of plants. Most cultivars of maize are deficient in essential amino acids such as lysine and tryptophan. Here, we measured the levels of 17 different total amino acids, and created 48 derived traits in mature kernels from a maize diversity inbred collection and three recombinant inbred line (RIL) populations. By GWAS, 247 and 281 significant loci were identified in two different environments, 5...
February 20, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28218759/limited-statistical-evidence-for-shared-genetic-effects-of-eqtls-and-autoimmune-disease-associated-loci-in-three-major-immune-cell-types
#13
Sung Chun, Alexandra Casparino, Nikolaos A Patsopoulos, Damien C Croteau-Chonka, Benjamin A Raby, Philip L De Jager, Shamil R Sunyaev, Chris Cotsapas
Most autoimmune-disease-risk effects identified by genome-wide association studies (GWAS) localize to open chromatin with gene-regulatory activity. GWAS loci are also enriched in expression quantitative trait loci (eQTLs), thus suggesting that most risk variants alter gene expression. However, because causal variants are difficult to identify, and cis-eQTLs occur frequently, it remains challenging to identify specific instances of disease-relevant changes to gene regulation. Here, we used a novel joint likelihood framework with higher resolution than that of previous methods to identify loci where autoimmune-disease risk and an eQTL are driven by a single shared genetic effect...
February 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28217939/pitx2-dependent-gene-regulation-in-atrial-fibrillation-and-rhythm-control
#14
Fahima Syeda, Paulus Kirchhof, Larissa Fabritz
Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. There are several major mechanisms that cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies (GWAS) have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription factor PITX2. The effect of these common gene variants on cardiac PITX2 mRNA is currently under study...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28217245/genome-wide-association-test-of-multiple-continuous-traits-using-imputed-snps
#15
Baolin Wu, James S Pankow
More and more large cohort studies have conducted or are conducting genome-wide association studies (GWAS) to reveal the genetic components of many complex human diseases. These large cohort studies often collected a broad array of correlated phenotypes that reflect common physiological processes. By jointly analyzing these correlated traits, we can gain more power by aggregating multiple weak effects and shed light on the mechanisms underlying complex human diseases. The majority of existing multi-trait association test methods are based on jointly modeling the multivariate traits conditional on the genotype as covariate, and can readily accommodate the imputed SNPs by using their imputed dosage as a covariate...
2017: Statistics and its Interface
https://www.readbyqxmd.com/read/28215025/analysis-of-the-genetic-architecture-of-maize-ear-and-grain-morphological-traits-by-combined-linkage-and-association-mapping
#16
Chaoshu Zhang, Zhiqiang Zhou, Hongjun Yong, Xiaochong Zhang, Zhuanfang Hao, Fangjun Zhang, Mingshun Li, Degui Zhang, Xinhai Li, Zhenhua Wang, Jianfeng Weng
Using combined linkage and association mapping, 26 stable QTL and six stable SNPs were detected across multiple environments for eight ear and grain morphological traits in maize. One QTL, PKS2, might play an important role in maize yield improvement. In the present study, one bi-parental population and an association panel were used to identify quantitative trait loci (QTL) for eight ear and grain morphological traits. A total of 108 QTL related to these traits were detected across four environments using an ultra-high density bin map constructed using recombinant inbred lines (RILs) derived from a cross between Ye478 and Qi319, and 26 QTL were identified in more than two environments...
February 18, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28212402/graph-gpa-a-graphical-model-for-prioritizing-gwas-results-and-investigating-pleiotropic-architecture
#17
Dongjun Chung, Hang J Kim, Hongyu Zhao
Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. However, identification of risk variants associated with complex diseases remains challenging as they are often affected by many genetic variants with small or moderate effects. There has been accumulating evidence suggesting that different complex traits share common risk basis, namely pleiotropy...
February 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#18
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28211582/what-can-genome-wide-association-studies-tell-us-about-the-evolutionary-forces-maintaining-genetic-variation-for-quantitative-traits
#19
REVIEW
Emily B Josephs, John R Stinchcombe, Stephen I Wright
Contents 21 I. 21 II. 22 III. 24 IV. 25 V. 29 30 References 30 SUMMARY: Understanding the evolutionary forces that shape genetic variation within species has long been a goal of evolutionary biology. Integrating data for the genetic architecture of traits from genome-wide association mapping studies (GWAS) along with the development of new population genetic methods for identifying selection in sequence data may allow us to evaluate the roles of mutation-selection balance and balancing selection in shaping genetic variation at various scales...
April 2017: New Phytologist
https://www.readbyqxmd.com/read/28208589/association-of-lpp-and-tagap-polymorphisms-with-celiac-disease-risk-a-meta-analysis
#20
Shi-Qi Huang, Na Zhang, Zi-Xing Zhou, Chui-Can Huang, Cheng-Li Zeng, Di Xiao, Cong-Cong Guo, Ya-Jing Han, Xiao-Hong Ye, Xing-Guang Ye, Mei-Ling Ou, Bao-Huan Zhang, Yang Liu, Eddy Y Zeng, Guang Yang, Chun-Xia Jing
Background: Lipoma preferred partner (LPP) and T-cell activation Rho GTPase activating protein (TAGAP) polymorphisms might influence the susceptibility to celiac disease. Therefore, we performed a meta-analysis by identifying relevant studies to estimate the risks of these polymorphisms on celiac disease. Methods: The PubMed, Web of Science and Embase databases were searched (up to October 2016) for LPP rs1464510 and TAGAP rs1738074 polymorphisms. Results: This meta-analysis included the same 7 studies for LPP rs1464510 and TAGAP rs1738074...
February 10, 2017: International Journal of Environmental Research and Public Health
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