Evaluation of next generation sequencing platforms for population targeted sequencing studies (2009)
Harismendy, Olivier, Ng, Pauline C, Strausberg, Robert L, Wang, Xiaoyun, Stockwell, Timothy B, Beeson, Karen Y, ...
Abstract Background Next generation sequencing (NGS) platforms are currently being utilized for targeted sequencing of candidate genes or genomic intervals to perform sequence-based association...
Prestige centrality-based functional outlier detection in gene expression analysis (2009)
Torkamani, Ali, Schork, Nicholas J.
Motivation: Traditional gene expression analysis techniques capture an average gene expression state across sample replicates. However, the average signal across replicates will not capture activated...
Identification of rare cancer driver mutations by network reconstruction (2009)
Torkamani, Ali, Schork, Nicholas J.
Recent large-scale tumor resequencing studies have identified a number of mutations that might be involved in tumorigenesis. Analysis of the frequency of specific mutations across different tumors...
Ali Torkamani, Nicholas J. Schork, Prof Martin Bishop
Motivation: Contemporary, high-throughput sequencing efforts have identified a rich source of naturally occurring single nucleotide polymorphisms (SNPs), a subset of which occur in the coding region...
Detecting genetic variation in microarray expression data (2007)
Greenhall, Jennifer A., Zapala, Matthew A., Cáceres, Mario, Libiger, Ondrej, Barlow, Carrolee, Schork, Nicholas J., ...
The use of high-density oligonucleotide arrays to measure the expression levels of thousands of genes in parallel has become commonplace. To take further advantage of the growing body of data, we...
Wen, Gen, Wessel, Jennifer, Zhou, Weidong, Ehret, Georg B., Rao, Fangwen, Stridsberg, Mats, ...
Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence...
Generalized Analysis of Molecular Variance (2007)
Caroline M. Nievergelt, Ondrej Libiger, Nicholas J. Schork
Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for...
Hovatta, Iiris, Zapala, Matthew A, Broide, Ron S, Schadt, Eric E, Libiger, Ondrej, Schork, Nicholas J, ...
Abstract Background Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies,...
Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans (2007)
Luo, Xingguang, Kranzler, Henry R., Zuo, Lingjun, Wang, Shuang, Schork, Nicholas J., Gelernter, Joel
Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with...
Braff, David L., Freedman, Robert, Schork, Nicholas J., Gottesman, Irving I.
The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of...
Calkins, Monica E., Dobie, Dorcas J., Cadenhead, Kristin S., Olincy, Ann, Freedman, Robert, Green, Michael F., ...
Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health–funded, 7-site collaboration investigating the occurrence and genetic...
Schork, Nicholas J., Greenwood, Tiffany A., Braff, David L.
Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence...
Accurate prediction of deleterious protein kinase polymorphisms (2007)
Torkamani, Ali, Schork, Nicholas J.
Motivation: Contemporary, high-throughput sequencing efforts have identified a rich source of naturally occurring single nucleotide polymorphisms (SNPs), a subset of which occur in the coding region...
Calkins, Monica E., Dobie, Dorcas J., Cadenhead, Kristin S., Olincy, Ann, Freedman, Robert, Green, Michael F., ...
Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic...
Schork, Nicholas J., Greenwood, Tiffany A., Braff, David L.
Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence...
Braff, David L., Freedman, Robert, Schork, Nicholas J., Gottesman, Irving I.
The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of...
Multiple ADH genes modulate risk for drug dependence (2006)
Luo, Xingguang, Kranzler, Henry R., Zuo, Lingjun, Wang, Shuang, Schork, Nicholas J., Gelernter, Joel
Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many studies have also shown common genetic risk factors for these disorders. We previously reported associations of AD with...
Simulation-based homozygosity mapping with the GAW14 COGA dataset on alcoholism (2005)
Libiger, Ondrej, Schork, Nicholas J
Abstract Background We have developed a simulation-based approach to the analysis of shared homozygous chromosomal segments and have applied it to data on allele sharing among alcoholics in a single...
Tang, Hua, Quertermous, Tom, Rodriguez, Beatriz, Kardia, Sharon LR, Zhu, Xiaofeng, Brown, Andrew, ...
We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension...
Soares, Miguel L., Coelho, Teresa, Sousa, Alda, Batalov, Serge, Conceição, Isabel, Sales-Luís, Maria L., ...
Familial amyloid polyneuropathy type I is an autosomal dominant disorder caused by mutations in the transthyretin (TTR) gene; however, carriers of the same mutation exhibit variability in penetrance...
Large-Scale Integration of Human Genetic and Physical Maps (2004)
Nievergelt, Caroline M., Smith, Douglas W., Kohlenberg, J. Bradley, Schork, Nicholas J.
Genetic maps are used routinely in family-based linkage studies to identify the rough location of genes that influence human traits and diseases. Unlike physical maps, genetic maps are based on the...
Human Haplotype Block Sizes Are Negatively Correlated With Recombination Rates (2004)
Greenwood, Tiffany A., Rana, Brinda K., Schork, Nicholas J.
The International Haplotype Map (“HapMap”) Project is motivated, in part, by the belief that the organization of the human genome, the mechanics of recombination, and the population-level...
Large-Scale Integration of Human Genetic and Physical Maps (2004)
Nievergelt, Caroline M., Smith, Douglas W., Kohlenberg, J. Bradley, Schork, Nicholas J.
Genetic maps are used routinely in family-based linkage studies to identify the rough location of genes that influence human traits and diseases. Unlike physical maps, genetic maps are based on the...
Segregation Analysis of Blood Pressure and Body Mass Index in a Rural US Community (2002)
Chakravarti, Aravinda., Chen, Chien-Hsiun., Cooper, Richard., Weder, Alan., Schork, Nicholas J.
Human Biology - Volume 74, Number 1, February 2002
Fallin, Daniele, Cohen, Annick, Essioux, Laurent, Chumakov, Ilya, Blumenfeld, Marta, Cohen, Daniel, ...
There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as...
Fallin, Daniele, Cohen, Annick, Essioux, Laurent, Chumakov, Ilya, Blumenfeld, Marta, Cohen, Daniel, ...
Fallin, Daniele, Schork, Nicholas J.
Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes....
Schork, Nicholas J., Nath, Swapan K., Fallin, Daniele, Chakravarti, Aravinda
Linkage disequilibrium (LD) mapping has been applied to many simple, monogenic, overtly Mendelian human traits, with great success. However, extensions and applications of LD mapping approaches to...
Ginns, Edward I., St. Jean, Pamela, Philibert, Robert A., Galdzicka, Marzena, Damschroder-Williams, Patricia, Thiel, Bonnie, ...
Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant...
Bix, Mark, Wang, Zhi-En, Thiel, Bonnie, Schork, Nicholas J., Locksley, Richard M.
The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4...
Overt computational constraints in the formation of mixed models for the analysis of large extended-pedigree quantitative trait data which allow one to reliably characterize and partition sources of...
Detection of genetic heterogeneity for complex quantitative phenotypes (1992)
Statistically characterizing factors responsible for quantitative phenotype expression (e.g., polygenes, major genes, shared household factors, etc.) through model selection strategies is a difficult...
On the asymmetry of biological frequency distributions (1990)
Schork, Nicholas J., Weder, Alan B., Schork, M. Anthony
The long-standing problem of determining whether the skewness in a sample frequency distribution is the manifestation of the intermixing of disparate groups characterizable by a normal mixture...
Kjeldsen, Sverre E., Schork, Nicholas J., Leren, Paul, Eide, Ivar K.
Increased plasma catecholamine levels assessed from the venous blood have been found in a number of studies of younger patients with essential hypertension, but hypertensive-normotensive differences...
Gupta, Madhulika A., Gupta, Aditya K., Kirkby, Sueann, Schork, Nicholas J., Gorr, Susan K., Ellis, Charles N., ...
Psoriasis is a chronic, relapsing, cutaneous condition with a 1%-2% prevalence in the general population. About 40% of psoriatics report that psychosocial stress significantly exacerbates their...
Johnson, Ernest H., Schork, Nicholas J., Spielberger, Charles D.
The relationship between various measures of the expression and experience of anger (and anxiety), traditional risk factors and blood pressure were examined in a sample of black and white female...
Ginns, Edward I., St. Jean, Pamela, Philibert, Robert A., Galdzicka, Marzena, Damschroder-Williams, Patricia, Thiel, Bonnie, ...
Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant...
Fallin, Daniele, Cohen, Annick, Essioux, Laurent, Chumakov, Ilya, Blumenfeld, Marta, Cohen, Daniel, ...
There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as...
Large-Scale Integration of Human Genetic and Physical Maps
Nievergelt, Caroline M., Smith, Douglas W., Kohlenberg, J. Bradley, Schork, Nicholas J.
Genetic maps are used routinely in family-based linkage studies to identify the rough location of genes that influence human traits and diseases. Unlike physical maps, genetic maps are based on the...
Human Haplotype Block Sizes Are Negatively Correlated With Recombination Rates
Greenwood, Tiffany A., Rana, Brinda K., Schork, Nicholas J.
The International Haplotype Map (“HapMap”) Project is motivated, in part, by the belief that the organization of the human genome, the mechanics of recombination, and the population-level...
Fallin, Daniele, Schork, Nicholas J.
Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes....
Schork, Nicholas J., Nath, Swapan K., Fallin, Daniele, Chakravarti, Aravinda
Linkage disequilibrium (LD) mapping has been applied to many simple, monogenic, overtly Mendelian human traits, with great success. However, extensions and applications of LD mapping approaches to...
Luo, Xingguang, Kranzler, Henry R., Zuo, Lingjun, Wang, Shuang, Schork, Nicholas J., Gelernter, Joel
The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and...
Broeckel, Ulrich, Schork, Nicholas J
Understanding the mechanisms by which DNA and DNA variation influence diseases, naturally occurring phenotypic variation, and complex biological systems, has been one of the major tasks associated...
Ginns, Edward I., St. Jean, Pamela, Philibert, Robert A., Galdzicka, Marzena, Damschroder-Williams, Patricia, Thiel, Bonnie, ...
Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant...
Fallin, Daniele, Cohen, Annick, Essioux, Laurent, Chumakov, Ilya, Blumenfeld, Marta, Cohen, Daniel, ...
There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as...
Power Calculations for Genetic Association Studies Using Estimated Probability Distributions
The determination of the power of—or of an appropriate sample size for—genetic association studies that exploit linkage disequilibrium requires many assumptions. Some of the more important...
Large-Scale Integration of Human Genetic and Physical Maps
Nievergelt, Caroline M., Smith, Douglas W., Kohlenberg, J. Bradley, Schork, Nicholas J.
Genetic maps are used routinely in family-based linkage studies to identify the rough location of genes that influence human traits and diseases. Unlike physical maps, genetic maps are based on the...
Human Haplotype Block Sizes Are Negatively Correlated With Recombination Rates
Greenwood, Tiffany A., Rana, Brinda K., Schork, Nicholas J.
The International Haplotype Map (“HapMap”) Project is motivated, in part, by the belief that the organization of the human genome, the mechanics of recombination, and the population-level...
Wen, Gen, Mahata, Sushil K., Cadman, Peter, Mahata, Manjula, Ghosh, Sajalendu, Mahapatra, Nitish R., ...
The chromogranin/secretogranin proteins are costored and coreleased with catecholamines from secretory vesicles in chromaffin cells and noradrenergic neurons. Chromogranin A (CHGA) regulates...
Inherent Bias toward the Null Hypothesis in Conventional Multipoint Nonparametric Linkage Analysis
Schork, Nicholas J., Greenwood, Tiffany A.
Traditional nonparametric “multipoint” statistical procedures have been developed for assigning allele-sharing values at a locus of interest to pairs of relatives for linkage studies. These...
Tang, Hua, Quertermous, Tom, Rodriguez, Beatriz, Kardia, Sharon L. R., Zhu, Xiaofeng, Brown, Andrew, ...
We have analyzed genetic data for 326 microsatellite markers that were typed uniformly in a large multiethnic population-based sample of individuals as part of a study of the genetics of hypertension...
Reiner, Alexander P., Ziv, Elad, Lind, Denise L., Nievergelt, Caroline M., Schork, Nicholas J., Cummings, Steven R., ...
U.S. populations are genetically admixed, but surprisingly little empirical data exists documenting the impact of such heterogeneity on type I and type II error in genetic-association studies of...
Fallin, Daniele, Schork, Nicholas J.
Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes....
Schork, Nicholas J., Nath, Swapan K., Fallin, Daniele, Chakravarti, Aravinda
Linkage disequilibrium (LD) mapping has been applied to many simple, monogenic, overtly Mendelian human traits, with great success. However, extensions and applications of LD mapping approaches to...
Luo, Xingguang, Kranzler, Henry R., Zuo, Lingjun, Wang, Shuang, Schork, Nicholas J., Gelernter, Joel
The set of alcohol-metabolizing enzymes has considerable genetic and functional complexity. The relationships between some alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes and...
Broeckel, Ulrich, Schork, Nicholas J
Understanding the mechanisms by which DNA and DNA variation influence diseases, naturally occurring phenotypic variation, and complex biological systems, has been one of the major tasks associated...
Hovatta, Iiris, Zapala, Matthew A, Broide, Ron S, Schadt, Eric E, Libiger, Ondrej, Schork, Nicholas J, ...
Gene expression profiles of five brain regions from six inbred mouse strains suggest that many regulatory networks are highly specific to particular brain regions.
Generalized Analysis of Molecular Variance
Nievergelt, Caroline M, Libiger, Ondrej, Schork, Nicholas J
Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for...
Generalized Genomic Distance–Based Regression Methodology for Multilocus Association Analysis
Wessel, Jennifer, Schork, Nicholas J.
Large-scale, multilocus genetic association studies require powerful and appropriate statistical-analysis tools that are designed to relate genotype and haplotype information to phenotypes of...
Zapala, Matthew A., Schork, Nicholas J.
A fundamental step in the analysis of gene expression and other high-dimensional genomic data is the calculation of the similarity or distance between pairs of individual samples in a study. If one...
Zhang, Lian, Rao, Fangwen, Zhang, Kuixing, Khandrika, Srikrishna, Das, Madhusudan, Vaingankar, Sucheta M., ...
GTP cyclohydrolase 1 (GCH1) is rate limiting in the provision of the cofactor tetrahydrobiopterin for biosynthesis of catecholamines and NO. We asked whether common genetic variation at GCH1 alters...
Greenwood, Tiffany A., Libiger, Ondrej, Kardia, Sharon, Hanis, Craig, Morrison, Alanna C., Gu, C. Charles, ...
Linkage analyses of complex, multifactorial traits and diseases, such as essential hypertension, have been difficult to interpret and reconcile. Many published studies provide evidence suggesting...
Detecting genetic variation in microarray expression data
Greenhall, Jennifer A., Zapala, Matthew A., Cáceres, Mario, Libiger, Ondrej, Barlow, Carrolee, Schork, Nicholas J., ...
The use of high-density oligonucleotide arrays to measure the expression levels of thousands of genes in parallel has become commonplace. To take further advantage of the growing body of data, we...
Genetic Regulation of Commitment to Interleukin 4 Production by a CD4+ T Cell–intrinsic Mechanism
Bix, Mark, Wang, Zhi-En, Thiel, Bonnie, Schork, Nicholas J., Locksley, Richard M.
The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4...
Advances in endophenotyping schizophrenia
BRAFF, DAVID L., GREENWOOD, TIFFANY A., SWERDLOW, NEAL R., LIGHT, GREGORY A., SCHORK, NICHOLAS J.
The search for the genetic architecture of schizophrenia has employed multiple, often converging strategies. One such strategy entails the use of tracing the heritability and neurobiology of...
Mechanisms Underlying Hypoxia Tolerance in Drosophila melanogaster: hairy as a Metabolic Switch
Zhou, Dan, Xue, Jin, Lai, James C. K., Schork, Nicholas J., White, Kevin P., Haddad, Gabriel G.
Hypoxia-induced cell injury has been related to multiple pathological conditions. In order to render hypoxia-sensitive cells and tissues resistant to low O2 environment, in this current study, we...
Congenital disease SNPs target lineage specific structural elements in protein kinases
Torkamani, Ali, Kannan, Natarajan, Taylor, Susan S., Schork, Nicholas J.
The catalytic domain of protein kinases harbors a large number of disease-causing single nucleotide polymorphisms (SNPs) and common or neutral SNPs that are not known or hypothesized to be associated...
Statistical Genetics Concepts and Approaches in Schizophrenia and Related Neuropsychiatric Research
Schork, Nicholas J., Greenwood, Tiffany A., Braff, David L.
Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence...
Braff, David L., Freedman, Robert, Schork, Nicholas J., Gottesman, Irving I.
The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of...
Calkins, Monica E., Dobie, Dorcas J., Cadenhead, Kristin S., Olincy, Ann, Freedman, Robert, Green, Michael F., ...
Background: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health–funded, 7-site collaboration investigating the occurrence and genetic...
Chromogranin A Polymorphisms Are Associated With Hypertensive Renal Disease
Salem, Rany M., Cadman, Peter E., Chen, Yuqing, Rao, Fangwen, Wen, Gen, Hamilton, Bruce A., ...
Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments,...
Accommodating Linkage Disequilibrium in Genetic-Association Analyses via Ridge Regression
Malo, Nathalie, Libiger, Ondrej, Schork, Nicholas J.
Large-scale genetic-association studies that take advantage of an extremely dense set of genetic markers have begun to produce very compelling statistical associations between multiple makers...
Evaluation of next generation sequencing platforms for population targeted sequencing studies
Harismendy, Olivier, Ng, Pauline C, Strausberg, Robert L, Wang, Xiaoyun, Stockwell, Timothy B, Beeson, Karen Y, ...
Human sequence generated from three next-generation sequencing platforms reveals systematic variability in sequence coverage due to local sequence characteristics.
Predicting functional regulatory polymorphisms
Torkamani, Ali, Schork, Nicholas J.
Motivation: Limited availability of data has hindered the development of algorithms that can identify functionally meaningful regulatory single nucleotide polymorphisms (rSNPs). Given the large...
Sequence and Structure Signatures of Cancer Mutation Hotspots in Protein Kinases
Dixit, Anshuman, Yi, Lin, Gowthaman, Ragul, Torkamani, Ali, Schork, Nicholas J., Verkhivker, Gennady M.
Protein kinases are the most common protein domains implicated in cancer, where somatically acquired mutations are known to be functionally linked to a variety of cancers. Resequencing studies of...