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Missing heritability

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https://www.readbyqxmd.com/read/28095416/meta-gwas-accuracy-and-power-metagap-calculator-shows-that-hiding-heritability-is-partially-due-to-imperfect-genetic-correlations-across-studies
#1
Ronald de Vlaming, Aysu Okbay, Cornelius A Rietveld, Magnus Johannesson, Patrik K E Magnusson, André G Uitterlinden, Frank J A van Rooij, Albert Hofman, Patrick J F Groenen, A Roy Thurik, Philipp D Koellinger
Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called 'missing heritability'. Here, we describe the online Meta-GWAS Accuracy and Power (MetaGAP) calculator (available at www...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28065468/the-genetic-architecture-of-gene-expression-in-peripheral-blood
#2
Luke R Lloyd-Jones, Alexander Holloway, Allan McRae, Jian Yang, Kerrin Small, Biao Zeng, Andrew Bakshi, Andres Metspalu, Manolis Dermitzakis, Greg Gibson, Tim Spector, Grant Montgomery, Tonu Esko, Peter M Visscher, Joseph E Powell
We analyzed the mRNA levels for 36,778 transcript expression traits (probes) from 2,765 individuals to comprehensively investigate the genetic architecture and degree of missing heritability for gene expression in peripheral blood. We identified 11,204 cis and 3,791 trans independent expression quantitative trait loci (eQTL) by using linear mixed models to perform genome-wide association analyses. Furthermore, using information on both closely and distantly related individuals, heritability was estimated for all expression traits...
December 24, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28039885/rare-variant-association-test-with-multiple-phenotypes
#3
Selyeong Lee, Sungho Won, Young Jin Kim, Yongkang Kim, Bong-Jo Kim, Taesung Park
Although genome-wide association studies (GWAS) have now discovered thousands of genetic variants associated with common traits, such variants cannot explain the large degree of "missing heritability," likely due to rare variants. The advent of next generation sequencing technology has allowed rare variant detection and association with common traits, often by investigating specific genomic regions for rare variant effects on a trait. Although multiple correlated phenotypes are often concurrently observed in GWAS, most studies analyze only single phenotypes, which may lessen statistical power...
December 31, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/28028462/network-based-analysis-of-differentially-expressed-genes-in-cerebrospinal-fluid-csf-and-blood-reveals-new-candidate-genes-for-multiple-sclerosis
#4
Nahid Safari-Alighiarloo, Mostafa Rezaei-Tavirani, Mohammad Taghizadeh, Seyyed Mohammad Tabatabaei, Saeed Namaki
BACKGROUND: The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein-protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. METHODS: Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed...
2016: PeerJ
https://www.readbyqxmd.com/read/27995669/perch-a-unified-framework-for-disease-gene-prioritization
#5
Bing-Jian Feng
To interpret genetic variants discovered from next-generation sequencing (NGS), integration of heterogeneous information is vital for success. This paper describes a framework named PERCH (Polymorphism Evaluation, Ranking, and Classification for a Heritable trait), available at http://BJFengLab.org/. It can prioritize disease genes by quantitatively unifying a new deleteriousness measure called BayesDel, an improved assessment of the biological relevance of genes to the disease, a modified linkage analysis, a novel rare-variant association test, and a converted variant call quality score...
December 19, 2016: Human Mutation
https://www.readbyqxmd.com/read/27903611/the-genomic-architecture-of-interactions-between-natural-genetic-polymorphisms-and-environments-in-yeast-growth
#6
Xinzhu Wei, Jianzhi Zhang
Gene-environment interaction (G×E) refers to the phenomenon that the same mutation has different phenotypic effects in different environments. Although quantitative trait loci (QTLs) exhibiting G×E have been reported, little is known about the general properties of G×E and those of its underlying QTLs. Here we use the genotypes of 1005 segregants from a cross between two Saccharomyces cerevisiae strains and the growth rates of these segregants in 47 environments to identify growth rate QTLs (gQTLs) in each environment and QTLs that have different growth effects in each pair of environments (g×eQTLs)...
November 30, 2016: Genetics
https://www.readbyqxmd.com/read/27896934/increased-identification-of-novel-variants-in-type-2-diabetes-birth-weight-and-their-pleiotropic-loci
#7
Chun-Ping Zeng, Yuan-Cheng Chen, Xu Lin, Jonathan Greenbaum, You-Ping Chen, Cheng Peng, Xia-Fang Wang, Rou Zhou, Wei-Min Deng, Jie Shen, Hong-Wen Deng
BACKGROUND: Clinical and epidemiological findings point to an association between type 2 diabetes (T2D) and low birth weight (BW). However, the nature underlying their relationship is largely unknown. Here, we aim to identify novel single-nucleotide polymorphisms (SNPs) in T2D, BW and their pleiotropic loci. METHODS: We applied a pleiotropy-informed conditional false discovery rate (cFDR) method to two independent GWAS summary statistics of T2D (n = 149,821) and BW (n = 26,836)...
November 29, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27888432/candidate-predisposing-germline-copy-number-variants-in-early-onset-colorectal-cancer-patients
#8
A J Brea-Fernandez, C Fernandez-Rozadilla, M Alvarez-Barona, D Azuara, M M Ginesta, J Clofent, L de Castro, D Gonzalez, M Andreu, X Bessa, X Llor, R Xicola, R Jover, A Castells, S Castellvi-Bel, G Capella, A Carracedo, C Ruiz-Ponte
PURPOSE: A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset. METHODS/PATIENTS: We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype...
November 25, 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27883230/missing-heritability-illegitimate-quantitative-comparison-of-holistic-and-reductionist-data-response-to-doi-10-1002-bies-201600084
#9
Eugene Sverdlov
No abstract text is available yet for this article.
December 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27859906/human-recq-helicase-pathogenic-variants-population-variation-and-missing-diseases
#10
Wenqing Fu, Alessio Ligabue, Kai J Rogers, Joshua M Akey, Raymond J Monnat
Heritable loss of function mutations in the human RECQ helicase genes BLM, WRN, and RECQL4 cause Bloom, Werner, and Rothmund-Thomson syndromes, cancer predispositions with additional developmental or progeroid features. In order to better understand RECQ pathogenic and population variation, we systematically analyzed genetic variation in all five human RECQ helicase genes. A total of 3,741 unique base pair-level variants were identified, across 17,605 potential mutation sites. Direct counting of BLM, RECQL4, and WRN pathogenic variants was used to determine aggregate and disease-specific carrier frequencies...
February 2017: Human Mutation
https://www.readbyqxmd.com/read/27852354/exploring-the-genetic-etiology-of-trust-in-adolescents-combined-twin-and-dna-analyses
#11
Robyn E Wootton, Oliver S P Davis, Abigail L Mottershaw, R Adele H Wang, Claire M A Haworth
Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom's Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends...
December 2016: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://www.readbyqxmd.com/read/27848076/identifying-gene-gene-interactions-that-are-highly-associated-with-four-quantitative-lipid-traits-across-multiple-cohorts
#12
Rishika De, Shefali S Verma, Emily Holzinger, Molly Hall, Amber Burt, David S Carrell, David R Crosslin, Gail P Jarvik, Helena Kuivaniemi, Iftikhar J Kullo, Leslie A Lange, Matthew B Lanktree, Eric B Larson, Kari E North, Alex P Reiner, Vinicius Tragante, Gerard Tromp, James G Wilson, Folkert W Asselbergs, Fotios Drenos, Jason H Moore, Marylyn D Ritchie, Brendan Keating, Diane Gilbert-Diamond
Genetic loci explain only 25-30 % of the heritability observed in plasma lipid traits. Epistasis, or gene-gene interactions may contribute to a portion of this missing heritability. Using the genetic data from five NHLBI cohorts of 24,837 individuals, we combined the use of the quantitative multifactor dimensionality reduction (QMDR) algorithm with two SNP-filtering methods to exhaustively search for SNP-SNP interactions that are associated with HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG)...
November 15, 2016: Human Genetics
https://www.readbyqxmd.com/read/27830690/-detection-of-novel-genetic-markers-of-susceptibility-to-preeclampsia-based-on-an-analysis-of-the-regulatory-genes-in-the-placental-tissue
#13
V N Serebrova, E A Trifonova, T V Gabidulina, I Yu Bukharina, T A Agarkova, I D Evtushenko, N R Maksimova, V A Stepanov
Regulatory single nucleotide polymorphisms (rSNPs) are the least-studied group of SNP; however, they play an essential role in the development of human pathology by altering the level of candidate genes expression. In this work, we analyzed 29 rSNPs in 17 new candidate genes associated with preeclampsia (PE) according to the analysis of the transcriptome in placental tissue. Three ethnic groups have been studied (yakut, russian, and buryat). We have detected significant associations of PE with eight rSNPs in six differentially expressed genes, i...
September 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27808177/a-short-insertion-mutation-disrupts-genesis-of-mir-16-and-causes-increased-body-weight-in-domesticated-chicken
#14
Xinzheng Jia, Huiran Lin, Qinghua Nie, Xiquan Zhang, Susan J Lamont
Body weight is one of the most important quantitative traits with high heritability in chicken. We previously mapped a quantitative trait locus (QTL) for body weight by genome-wide association study (GWAS) in an F2 chicken resource population. To identify the causal mutations linked to this QTL, expression profiles were determined on livers of high-weight and low-weight chicken lines by microarray. Combining the expression pattern with SNP effects by GWAS, miR-16 was identified as the most likely potential candidate with a 3...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799157/prevalence-and-penetrance-of-major-genes-and-polygenes-for-colorectal-cancer
#15
Aung Ko Win, Mark A Jenkins, James G Dowty, Antonis C Antoniou, Andrew Lee, Graham G Giles, Daniel D Buchanan, Mark Clendenning, Christophe Rosty, Dennis J Ahnen, Stephen N Thibodeau, Graham Casey, Steven Gallinger, Loic Le Marchand, Robert W Haile, John D Potter, Yingye Zheng, Noralane M Lindor, Polly A Newcomb, John L Hopper, Robert J MacInnis
BACKGROUND: While high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not known. METHODS: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the USA, Canada and Australia and screened probands for mutations in mismatch repair genes and MUTYH...
October 31, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27789554/lnc-ing-notch1-to-idiopathic-calcific-aortic-valve-disease
#16
EDITORIAL
W David Merryman, Cynthia R Clark
No abstract text is available yet for this article.
December 6, 2016: Circulation
https://www.readbyqxmd.com/read/27777418/the-phf21b-gene-is-associated-with-major-depression-and-modulates-the-stress-response
#17
M-L Wong, M Arcos-Burgos, S Liu, J I Vélez, C Yu, B T Baune, M C Jawahar, V Arolt, U Dannlowski, A Chuah, G A Huttley, R Fogarty, M D Lewis, S R Bornstein, J Licinio
Major depressive disorder (MDD) affects around 350 million people worldwide; however, the underlying genetic basis remains largely unknown. In this study, we took into account that MDD is a gene-environment disorder, in which stress is a critical component, and used whole-genome screening of functional variants to investigate the 'missing heritability' in MDD. Genome-wide association studies (GWAS) using single- and multi-locus linear mixed-effect models were performed in a Los Angeles Mexican-American cohort (196 controls, 203 MDD) and in a replication European-ancestry cohort (499 controls, 473 MDD)...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27771416/candidate-gene-analysis-of-the-fibrinogen-phenotype-reveals-the-importance-of-polygenic-co-regulation
#18
H Toinét Cronjé, Cornelie Nienaber-Rousseau, Lizelle Zandberg, Tinashe Chikowore, Zelda de Lange, Tertia van Zyl, Marlien Pieters
Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties...
October 19, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27766458/evaluating-mendelian-nephrotic-syndrome-genes-for-evidence-for-risk-alleles-or-oligogenicity-that-explain-heritability
#19
Brendan D Crawford, Christopher E Gillies, Catherine C Robertson, Matthias Kretzler, Edgar Otto, Virginia Vega-Wagner, Matthew G Sampson
BACKGROUND: More than 30 genes can harbor rare exonic variants sufficient to cause nephrotic syndrome (NS), and the number of genes implicated in monogenic NS continues to grow. However, outside the first year of life, the majority of affected patients, particularly in ancestrally mixed populations, do not have a known monogenic form of NS. Even in those children classified with a monogenic form of NS, there is phenotypic heterogeneity. Thus, we have only discovered a fraction of the heritability of NS-the underlying genetic factors contributing to phenotypic variation...
October 20, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/27765491/a-novel-fuzzy-set-based-multifactor-dimensionality-reduction-method-for-detecting-gene-gene-interaction
#20
Hye-Young Jung, Sangseob Leem, Sungyoung Lee, Taesung Park
BACKGROUND: Gene-gene interaction (GGI) is one of the most popular approaches for finding the missing heritability of common complex traits in genetic association studies. The multifactor dimensionality reduction (MDR) method has been widely studied for detecting GGIs. In order to identify the best interaction model associated with disease susceptibility, MDR compares all possible genotype combinations in terms of their predictability of disease status from a simple binary high(H) and low(L) risk classification...
September 29, 2016: Computational Biology and Chemistry
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