28 results on '"Gayán, Javier"'
Search Results
2. Whole Genome Sequencing Identifies Novel Common and Low-Frequency Variants Associated With Age-Related Macular Degeneration
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Acar, Ilhan E., primary, Galesloot, Tessel E., additional, Luhmann, Ulrich F. O., additional, Fauser, Sascha, additional, Gayán, Javier, additional, den Hollander, Anneke I., additional, and Nogoceke, Everson, additional
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- 2023
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- View/download PDF
3. Correlation of Aqueous, Vitreous, and Serum Protein Levels in Patients With Retinal Diseases
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Wilson, Sabine, primary, Siebourg-Polster, Juliane, additional, Titz, Bjoern, additional, Jiang, Zhiwen, additional, Bartolo, Francois, additional, Lavergne, Vincent, additional, Gayán, Javier, additional, Garweg, Justus G., additional, Fauser, Sascha, additional, and Dieckmann, Andreas, additional
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- 2023
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4. Approaching allelic probabilities and Genome-Wide Association Studies from beta distributions
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García-Cremades, José Santiago, del Río, Angel, García, José A., Gayán, Javier, González-Pérez, Antonio, Ruiz, Agustín, Sotolongo-Grau, O., and Ruiz-Marín, Manuel
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Quantitative Biology - Genomics ,Quantitative Biology - Populations and Evolution ,Statistics - Applications - Abstract
In this paper we have proposed a model for the distribution of allelic probabilities for generating populations as reliably as possible. Our objective was to develop such a model which would allow simulating allelic probabilities with different observed truncation and de- gree of noise. In addition, we have also introduced here a complete new approach to analyze a genome-wide association study (GWAS) dataset, starting from a new test of association with a statistical distribution and two effect sizes of each genotype. The new methodologi- cal approach was applied to a real data set together with a Monte Carlo experiment which showed the power performance of our new method. Finally, we compared the new method based on beta distribution with the conventional method (based on Chi-Squared distribu- tion) using the agreement Kappa index and a principal component analysis (PCA). Both the analyses show found differences existed between both the approaches while selecting the single nucleotide polymorphisms (SNPs) in association., Comment: 24 pages, 16 figures, to be submitted to publication
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- 2014
5. Etiology of Reading Difficulties and Rapid Naming: The Colorado Twin Study of Reading Disability
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Davis, Chayna J., Gayán, Javier, Knopik, Valerie S., Smith, Shelley D., Cardon, Lon R., Pennington, Bruce F., Olson, Richard K., and DeFries, John C.
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- 2001
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6. The Relationship Between CAG Repeat Length and Age of Onset Differs for Huntingtonʼs Disease Patients with Juvenile Onset or Adult Onset
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Andresen, J. Michael, Gayán, Javier, Djoussé, Luc, Roberts, Simone, Brocklebank, Denise, Cherny, Stacey S., Cardon, Lon R., Gusella, James F., MacDonald, Marcy E., Myers, Richard H., Housman, David E., and Wexler, Nancy S.
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- 2007
7. WWOX gene is associated with HDL cholesterol and triglyceride levels
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Serrano-Ríos Manuel, Real Luis M, Gayán Javier, Martínez-Larrad María T, González-Pérez Antonio, Sáez María E, and Ruiz Agustín
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Altered lipid profile, and in particular low HDL and high triglyceride (TG) plasma levels, are within the major determinants of cardiovascular diseases. The identification of quantitative trait loci (QTL) affecting these lipid levels is a relevant issue for predictive purposes. The WWOX gene has been recently associated with HDL levels. This gene is located at chromosome 16q23, a region previously linked to familial combined hyperlipidemia (FCHL) and HDL. Our objective is to perform a genetic association analysis at the WWOX gene region with HDL, TG and TG/HDL ratio. Methods A quantitative association analysis performed in 801 individuals selected from the Spanish general population. Results For HDL levels, two regions of intron 8 display clustering of positive signals (p < 0.05) but none of them was associated in the haplotypic analysis (0.07 ≤ p ≤ 0.165). For TG levels not only intron 8 but also a 27 kb region spanning from the promoter region to intron 4 are associated in this study. For the TG/HDL genetic association analysis, positive signals are coincident with those of the isolated traits. Interestingly, haplotypic analysis at the 5' region showed that variation in this region modified both HDL and TG levels, especially the latter (p = 0.003). Conclusions Our results suggest that WWOX is a QTL for both TG and HDL.
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- 2010
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8. 'Does replication groups scoring reduce false positive rate in SNP interaction discovery?: Response'
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González-Pérez Antonio, Gayán Javier, and Ruiz Agustín
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract A response to Toplak et al: Does replication groups scoring reduce false positive rate in SNP interaction discovery? BMC Genomics 2010, 11:58. Background The genomewide evaluation of genetic epistasis is a computationally demanding task, and a current challenge in Genetics. HFCC (Hypothesis-Free Clinical Cloning) is one of the methods that have been suggested for genomewide epistasis analysis. In order to perform an exhaustive search of epistasis, HFCC has implemented several tools and data filters, such as the use of multiple replication groups, and direction of effect and control filters. A recent article has claimed that the use of multiple replication groups (as implemented in HFCC) does not reduce the false positive rate, and we hereby try to clarify these issues. Results/Discussion HFCC uses, as an analysis strategy, the possibility of replicating findings in multiple replication groups, in order to select a liberal subset of preliminary results that are above a statistical criterion and consistent in direction of effect. We show that the use of replication groups and the direction filter reduces the false positive rate of a study, although at the expense of lowering the overall power of the study. A post-hoc analysis of these selected signals in the combined sample could then be performed to select the most promising results. Conclusion Replication of results in independent samples is generally used in scientific studies to establish credibility in a finding. Nonetheless, the combined analysis of several datasets is known to be a preferable and more powerful strategy for the selection of top signals. HFCC is a flexible and complete analysis tool, and one of its analysis options combines these two strategies: A preliminary multiple replication group analysis to eliminate inconsistent false positive results, and a post-hoc combined-group analysis to select the top signals.
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- 2010
- Full Text
- View/download PDF
9. Genetic Structure of the Spanish Population
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Gutiérrez Marta, Ochoa María, Molero Eva, Ochoa Carolina, Carrasco José M, Velasco Juan, Moreno-Rey Concha, Royo Jose, Morón Francisco J, Ramírez-Lorca Reposo, Salinas Ana, Rivero M Carmen, Zabena Carina, Martínez-Larrad María, Sáez María, González-Pérez Antonio, Galan José J, Gayán Javier, Reina Mercedes, Pascual Rocío, Romo-Astorga Alejandro, Susillo-González Juan, Vázquez Enrique, Real Luis M, Ruiz Agustín, and Serrano-Ríos Manuel
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias. Results In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts. Conclusions In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.
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- 2010
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10. An entropy test for single-locus genetic association analysis
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González-Pérez Antonio, Romo-Astorga Alejandro, Susillo-González Juan, Cordoba José, Matilla-García Mariano, Ruiz-Marín Manuel, Ruiz Agustín, and Gayán Javier
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Genetics ,QH426-470 - Abstract
Abstract Background The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects Results We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with low-frequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF Conclusions We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial, since many researchers tend to discard low allele-frequency SNPs from their analysis. Now they can apply the same statistical test of association to all SNPs in a single analysis., which can be especially helpful to detect rare effects.
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- 2010
- Full Text
- View/download PDF
11. A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis
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Galan Jose, Quintas Antonio, Royo Jose, Sáez María, Bermudo Fernando, González-Pérez Antonio, Gayán Javier, Morón Francisco, Ramirez-Lorca Reposo, Real Luis, and Ruiz Agustín
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Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The difficulty in elucidating the genetic basis of complex diseases roots in the many factors that can affect the development of a disease. Some of these genetic effects may interact in complex ways, proving undetectable by current single-locus methodology. Results We have developed an analysis tool called Hypothesis Free Clinical Cloning (HFCC) to search for genome-wide epistasis in a case-control design. HFCC combines a relatively fast computing algorithm for genome-wide epistasis detection, with the flexibility to test a variety of different epistatic models in multi-locus combinations. HFCC has good power to detect multi-locus interactions simulated under a variety of genetic models and noise conditions. Most importantly, HFCC can accomplish exhaustive genome-wide epistasis search with large datasets as demonstrated with a 400,000 SNP set typed on a cohort of Parkinson's disease patients and controls. Conclusion With the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses.
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- 2008
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12. A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver
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Strunz, Tobias, primary, Grassmann, Felix, additional, Gayán, Javier, additional, Nahkuri, Satu, additional, Souza-Costa, Debora, additional, Maugeais, Cyrille, additional, Fauser, Sascha, additional, Nogoceke, Everson, additional, and Weber, Bernhard H. F., additional
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- 2018
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13. Late language emergence in 24 month twins: Heritable and increased risk for LLE in twins
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Rice, Mabel L., Zubrick, Stephen R., Taylor, Catherine L., Gayán, Javier, and Bontempo, Daniel E.
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Male ,Verbal Behavior ,Linguistics ,Twins, Monozygotic ,Environment ,Language Development ,Risk Assessment ,Vocabulary ,Article ,Semantics ,Phenotype ,Sex Factors ,Child, Preschool ,Twins, Dizygotic ,Humans ,Female ,Language Development Disorders ,Child Language ,Psychoacoustics - Abstract
This study investigated the etiology of late language emergence (LLE) in 24-month-old twins, considering possible twinning, zygosity, gender, and heritability effects for vocabulary and grammar phenotypes.A population-based sample of 473 twin pairs participated. Multilevel modeling estimated means and variances of vocabulary and grammar phenotypes, controlling for familiality. Heritability was estimated with DeFries-Fulker regression and variance components models to determine effects of heritability, shared environment, and nonshared environment.Twins had lower average language scores than norms for single-born children, with lower average performance for monozygotic than dizygotic twins and for boys than girls, although gender and zygosity did not interact. Gender did not predict LLE. Significant heritability was detected for vocabulary (0.26) and grammar phenotypes (0.52 and 0.43 for boys and girls, respectively) in the full sample and in the sample selected for LLE (0.42 and 0.44). LLE and the appearance of Word Combinations were also significantly heritable (0.22-0.23).The findings revealed an increased likelihood of LLE in twin toddlers compared with single-born children that is modulated by zygosity and gender differences. Heritability estimates are consistent with previous research for vocabulary and add further suggestion of heritable differences in early grammar acquisition.
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- 2014
14. ATP5H/KCTD2 locus is associated with Alzheimer's disease risk
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Boada, Mercè, Antúnez, Carmen, Ramírez Lorca, Repo, DeStefano, Anita L., González Pérez, A., Gayán, Javier, López Arrieta, Jesús, Ikram, M. Arfan, Hernández, Isabel, Marín, J., Galán, José Jorge, Bis, Joshua C., Mauleón, Ana, Rosende-Roca, Maitée, Moreno Rey, Concha, Gudnason, Vilmundur, Morón, Francisco Jesús, Velasco, Juan, Carrasco, José Miguel, Alegret, Montserrat, Espinosa, Ana, Vinyes, Georgina, Lafuente, Asunción, Vargas, Liliana, Fitzpatrick, Annette L., Launer, Lenore Joy, Sáez, María Eugenia, Vázquez, Enrique, Becker, James T., López, Oscar L., Serrano Ríos, Manuel, Tárraga, Lluís, van Duijn, Cornelia M., Real, Luis M., Seshadri, Sudha, Ruiz, Agustín, Universitat Autònoma de Barcelona, Radiology & Nuclear Medicine, and Epidemiology
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Male ,Genotyping Techniques ,SNP ,Locus (genetics) ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,molecular epidemiology ,Cohort Studies ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,medicine ,genomics ,Humans ,GWAS ,Computer Simulation ,Genetic Predisposition to Disease ,Molecular Biology ,Genotyping ,Genetic association ,Genetics ,Aged, 80 and over ,Odds ratio ,Genomics ,Middle Aged ,Alzheimer's disease ,medicine.disease ,3. Good health ,Psychiatry and Mental health ,Genetic Loci ,Molecular epidemiology ,Female ,Original Article ,Mitochondrial ADP, ATP Translocases ,Genome-Wide Association Study - Abstract
To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P
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- 2014
15. Neurexin and neuroligin genes in Alzheimer's disease
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Ruiz, Agustín, Martínez Mir, Amalia, González-Pérez, Antonio, Gayán, Javier, Antúnez, Carmen, Marín, Juan J., Boada, Mercè, López-Arrieta, Jesús, Fernández, Evaristo, Ramírez Lorca, Reposo, Sáez, María Eugenia, Scholl, Francisco G., and Real, Luis Miguel
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education - Abstract
Póster presentado en la 11th International Conference on Alzheimer's & Parkinson's Diseases, celebrada en Florencia del 6 al 10 de marzo de 2013.-- Alzheimers Disease Neuroimaging Inititive, [Objectives] The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD., [Methods] To explore this hypothesis we carried out a meta-analysis of five genome-wide association studies (GWAS) comprising 1256 SNPs in the NRXN1, NRXN2, NRXN3 and NLGN1 genes (3009 cases and 3006 control individuals) using PLINK software., [Results] We identified a marker in the NRXN3 gene (rs17757879) that showed a consistent protective effect in all GWAS, however the statistical significance obtained did not resist multiple testing corrections (OR=0.851, p=0.002). Nonetheless, gender analysis revealed that this effect was restricted to males. A replication study with SNP rs17757879 in a Spanish population (1785 cases and 1634 controls) confirmed this observation (OR=0.752, C.I.=0.570-0.991, p=0.042)., [Conclusions] We conclude that NRXN3 might have a role in susceptibility to AD in males (rs17757879, OR=0.742, 95% C.I.=0.632-0.872, p=0.00028, final meta-analysis).
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- 2013
16. A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis
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Real, Luis M., primary, Ruiz, Agustín, additional, Gayán, Javier, additional, González-Pérez, Antonio, additional, Sáez, María E., additional, Ramírez-Lorca, Reposo, additional, Morón, Francisco J., additional, Velasco, Juan, additional, Marginet-Flinch, Ruth, additional, Musulén, Eva, additional, Carrasco, José M., additional, Moreno-Rey, Concha, additional, Vázquez, Enrique, additional, Chaves-Conde, Manuel, additional, Moreno-Nogueira, Jose A., additional, Hidalgo-Pascual, Manuel, additional, Ferrero-Herrero, Eduardo, additional, Castellví-Bel, Sergi, additional, Castells, Antoni, additional, Fernandez-Rozadilla, Ceres, additional, Ruiz-Ponte, Clara, additional, Carracedo, Angel, additional, González, Beatriz, additional, Alonso, Sergio, additional, and Perucho, Manuel, additional
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- 2014
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17. Genome-Wide Association Study of Multiple Sclerosis Confirms a Novel Locus at 5p13.1
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Matesanz, Fuencisla, primary, González-Pérez, Antonio, additional, Lucas, Miguel, additional, Sanna, Serena, additional, Gayán, Javier, additional, Urcelay, Elena, additional, Zara, Ilenia, additional, Pitzalis, Maristella, additional, Cavanillas, María L., additional, Arroyo, Rafael, additional, Zoledziewska, Magdalena, additional, Marrosu, Marisa, additional, Fernández, Oscar, additional, Leyva, Laura, additional, Alcina, Antonio, additional, Fedetz, Maria, additional, Moreno-Rey, Concha, additional, Velasco, Juan, additional, Real, Luis M., additional, Ruiz-Peña, Juan Luis, additional, Cucca, Francesco, additional, Ruiz, Agustín, additional, and Izquierdo, Guillermo, additional
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- 2012
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18. Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations
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Alcina, Antonio, primary, Abad-Grau, María del Mar, additional, Fedetz, María, additional, Izquierdo, Guillermo, additional, Lucas, Miguel, additional, Fernández, Óscar, additional, Ndagire, Dorothy, additional, Catalá-Rabasa, Antonio, additional, Ruiz, Agustín, additional, Gayán, Javier, additional, Delgado, Concepción, additional, Arnal, Carmen, additional, and Matesanz, Fuencisla, additional
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- 2012
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19. WWOX gene is associated with HDL cholesterol and triglyceride levels
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Sáez, María E, primary, González-Pérez, Antonio, additional, Martínez-Larrad, María T, additional, Gayán, Javier, additional, Real, Luis M, additional, Serrano-Ríos, Manuel, additional, and Ruiz, Agustín, additional
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- 2010
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20. "Does replication groups scoring reduce false positive rate in SNP interaction discovery?: Response"
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Gayán, Javier, primary, González-Pérez, Antonio, additional, and Ruiz, Agustín, additional
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- 2010
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21. Genetic Structure of the Spanish Population
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Gayán, Javier, primary, Galan, José J, additional, González-Pérez, Antonio, additional, Sáez, María Eugenia, additional, Martínez-Larrad, María Teresa, additional, Zabena, Carina, additional, Rivero, M Carmen, additional, Salinas, Ana, additional, Ramírez-Lorca, Reposo, additional, Morón, Francisco J, additional, Royo, Jose Luis, additional, Moreno-Rey, Concha, additional, Velasco, Juan, additional, Carrasco, José M, additional, Molero, Eva, additional, Ochoa, Carolina, additional, Ochoa, María Dolores, additional, Gutiérrez, Marta, additional, Reina, Mercedes, additional, Pascual, Rocío, additional, Romo-Astorga, Alejandro, additional, Susillo-González, Juan Luis, additional, Vázquez, Enrique, additional, Real, Luis M, additional, Ruiz, Agustín, additional, and Serrano-Ríos, Manuel, additional
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- 2010
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22. Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment
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Rice, Mabel L., primary, Smith, Shelley D., additional, and Gayán, Javier, additional
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- 2009
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23. A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis
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Gayán, Javier, primary, González-Pérez, Antonio, additional, Bermudo, Fernando, additional, Sáez, María Eugenia, additional, Royo, Jose Luis, additional, Quintas, Antonio, additional, Galan, Jose Jorge, additional, Morón, Francisco Jesús, additional, Ramirez-Lorca, Reposo, additional, Real, Luis Miguel, additional, and Ruiz, Agustín, additional
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- 2008
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24. Quantitative-Trait Locus for Specific Language and Reading Deficits on Chromosome 6p
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Gayán, Javier, primary, Smith, Shelley D., additional, Cherny, Stacey S., additional, Cardon, Lon R., additional, Fulker, David W., additional, Brower, Amy M., additional, Olson, Richard K., additional, Pennington, Bruce F., additional, and DeFries, John C., additional
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- 1999
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25. The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease.
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Antúnez, Carmen, Boada, Mercè, González-Pérez, Antonio, Gayán, Javier, Ramírez-Lorca, Reposo, Marín, Juan, Hernández, Isabel, Moreno-Rey, Concha, Morón, Francisco Jesús, López-Arrieta, Jesús, Mauleón, Ana, Rosende-Roca, Maitée, Noguera-Perea, Fuensanta, Legaz-García, Agustina, Vivancos-Moreau, Laura, Velasco, Juan, Carrasco, José Miguel, Alegret, Montserrat, Antequera-Torres, Martirio, and Manzanares, Salvadora
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ALZHEIMER'S disease ,PRESENILE dementia ,CLEAN rooms ,META-analysis ,GENES - Abstract
Background: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genomewide association study (GWAS) in the Spanish population. Methods: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings. Results: Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genomewide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls). Conclusions: Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases. [ABSTRACT FROM AUTHOR]
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- 2011
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26. "Does replication groups scoring reduce falsepositive rate in SNP interaction discovery?:Response"
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Gayán, Javier, González-Pérez, Antonio, and Ruiz, Agustín
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- *
GENE expression , *GENOMICS , *MOLECULAR genetics , *GENETIC engineering , *GENETIC regulation - Abstract
A response to Toplak et al: Does replication groups scoring reduce false positive rate in SNP interaction discovery? BMC Genomics 2010, 11:58. Background: The genomewide evaluation of genetic epistasis is a computationally demanding task, and a current challenge in Genetics. HFCC (Hypothesis-Free Clinical Cloning) is one of the methods that have been suggested for genomewide epistasis analysis. In order to perform an exhaustive search of epistasis, HFCC has implemented several tools and data filters, such as the use of multiple replication groups, and direction of effect and control filters. A recent article has claimed that the use of multiple replication groups (as implemented in HFCC) does not reduce the false positive rate, and we hereby try to clarify these issues. Results/Discussion: HFCC uses, as an analysis strategy, the possibility of replicating findings in multiple replication groups, in order to select a liberal subset of preliminary results that are above a statistical criterion and consistent in direction of effect. We show that the use of replication groups and the direction filter reduces the false positive rate of a study, although at the expense of lowering the overall power of the study. A post-hoc analysis of these selected signals in the combined sample could then be performed to select the most promising results. Conclusion: Replication of results in independent samples is generally used in scientific studies to establish credibility in a finding. Nonetheless, the combined analysis of several datasets is known to be a preferable and more powerful strategy for the selection of top signals. HFCC is a flexible and complete analysis tool, and one of its analysis options combines these two strategies: A preliminary multiple replication group analysis to eliminate inconsistent false positive results, and a post-hoc combined-group analysis to select the top signals. [ABSTRACT FROM AUTHOR]
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- 2010
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27. An entropy test for single-locus genetic association analysis.
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Ruiz-Marín, Manuel, Matilla-García, Mariano, García Cordoba, José Antonio, Susillo-González, Juan Luis, Romo-Astorga, Alejandro, González-Pérez, Antonio, Ruiz, Agustín, and Gayán, Javier
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ETIOLOGY of diseases ,GENETICS ,SYMBOLIC dynamics ,ENTROPY ,GENE frequency - Abstract
Background: The etiology of complex diseases is due to the combination of genetic and environmental factors, usually many of them, and each with a small effect. The identification of these small-effect contributing factors is still a demanding task. Clearly, there is a need for more powerful tests of genetic association, and especially for the identification of rare effects Results: We introduce a new genetic association test based on symbolic dynamics and symbolic entropy. Using a freely available software, we have applied this entropy test, and a conventional test, to simulated and real datasets, to illustrate the method and estimate type I error and power. We have also compared this new entropy test to the Fisher exact test for assessment of association with low-frequency SNPs. The entropy test is generally more powerful than the conventional test, and can be significantly more powerful when the genotypic test is applied to low allele-frequency markers. We have also shown that both the Fisher and Entropy methods are optimal to test for association with lowfrequency SNPs (MAF around 1-5%), and both are conservative for very rare SNPs (MAF<1%) Conclusions: We have developed a new, simple, consistent and powerful test to detect genetic association of biallelic/ SNP markers in case-control data, by using symbolic dynamics and symbolic entropy as a measure of gene dependence. We also provide a standard asymptotic distribution of this test statistic. Given that the test is based on entropy measures, it avoids smoothed nonparametric estimation. The entropy test is generally as good or even more powerful than the conventional and Fisher tests. Furthermore, the entropy test is more computationally efficient than the Fisher's Exact test, especially for large number of markers. Therefore, this entropy-based test has the advantage of being optimal for most SNPs, regardless of their allele frequency (Minor Allele Frequency (MAF) between 1-50%). This property is quite beneficial, since many researchers tend to discard low allele-frequency SNPs from their analysis. Now they can apply the same statistical test of association to all SNPs in a single analysis., which can be especially helpful to detect rare effects. [ABSTRACT FROM AUTHOR]
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- 2010
- Full Text
- View/download PDF
28. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset.
- Author
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Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayán J, Brocklebank D, Cherny SS, Cardon LR, Gray J, Dlouhy SR, Wiktorski S, Hodes ME, Conneally PM, Penney JB, Gusella J, Cha JH, Irizarry M, Rosas D, Hersch S, Hollingsworth Z, MacDonald M, Young AB, Andresen JM, Housman DE, De Young MM, Bonilla E, Stillings T, Negrette A, Snodgrass SR, Martinez-Jaurrieta MD, Ramos-Arroyo MA, Bickham J, Ramos JS, Marshall F, Shoulson I, Rey GJ, Feigin A, Arnheim N, Acevedo-Cruz A, Acosta L, Alvir J, Fischbeck K, Thompson LM, Young A, Dure L, O'Brien CJ, Paulsen J, Brickman A, Krch D, Peery S, Hogarth P, Higgins DS Jr, and Landwehrmeyer B
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Child, Child, Preschool, Environment, Female, Humans, Huntington Disease epidemiology, Male, Middle Aged, Models, Genetic, Phenotype, Trinucleotide Repeat Expansion, Venezuela epidemiology, Huntington Disease etiology, Huntington Disease genetics
- Abstract
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HD, although substantial variability remains after controlling for repeat length. The Venezuelan HD kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HD kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation +/- SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximately 40% of the variance remaining in onset age is attributable to genes other than the HD gene and 60% is environmental.
- Published
- 2004
- Full Text
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