Browsing by Author "Lange, Christoph"

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    • Adjusting heterogeneous ascertainment bias for genetic association analysis with extended families 

      Park, Suyeon; Lee, Sungyoung; Lee, Young; Herold, Christine; Hooli, Basavaraj; Mullin, Kristina; Park, Taesung; Park, Changsoon; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph; Won, Sungho (BioMed Central, 2015)
      Background: In family-based association analysis, each family is typically ascertained from a single proband, which renders the effects of ascertainment bias heterogeneous among family members. This is contrary to case–control ...

    • An alternative hypothesis testing strategy for secondary phenotype data in case-control genetic association studies 

      Lutz, Sharon M.; Hokanson, John E.; Lange, Christoph (Frontiers Media S.A., 2014)
      Motivated by the challenges associated with accounting for the ascertainment when analyzing secondary phenotypes that are correlated with case-control status, Lin and Zeng have proposed a method that properly reflects the ...

    • The Association of a SNP Upstream of INSIG2 with Body Mass Index is Reproduced in Several but Not All Cohorts 

      Emilsson, Valur; Hinney, Anke; Heid, Iris M; Zhu, Xiaofeng; Thorleifsson, Gudmar; Gunnarsdottir, Steinunn; Walters, G. Bragi; Thorsteinsdottir, Unnur; Kong, Augustine; Gulcher, Jeffrey; Nguyen, Thuy Trang; Scherag, André; Pfeufer, Arne; Meitinger, Thomas; Brönner, Günter; Rief, Winfried; Soto-Quiros, Manuel E; Avila, Lydiana; Groop, Leif; Tuomi, Tiinamaija; Isomaa, Bo; Bengtsson, Kristina; Butler, Johannah L; Vollmert, Caren; Celedón, Juan C; Wichmann, H. Erich; Hebebrand, Johannes; Stefansson, Kari; Abecasis, Gonçalo; Lyon, Helen N; Su, Jessica Ann Lasky; Klanderman, Barbara Jordan; Raby, Benjamin Alexander; Silverman, Edwin Kepner; Weiss, Scott Tillman; Laird, Nan M.; Ding, Xiao; Cooper, Richard S; Fox, Caroline; O'Donnell, Christopher Joseph; Lange, Christoph; Hirschhorn, Joel Naom (Public Library of Science, 2007)
      A SNP upstream of the INSIG2 gene, rs7566605, was recently found to be associated with obesity as measured by body mass index (BMI) by Herbert and colleagues. The association between increased BMI and homozygosity for the ...

    • Asthma-susceptibility variants identified using probands in case-control and family-based analyses 

      Murphy, Amy J; Soto-Quiros, Manuel E; Avila, Lydiana; Celedón, Juan C; O'Connor, George T; Himes, Blanca Elena; Su, Jessica Ann Lasky; Wu, Ann Chen; Wilk, Jemma B; Hunninghake, Gary Matthew; Klanderman, Barbara Jordan; Lazarus, Ross; Lange, Christoph; Raby, Benjamin Alexander; Silverman, Edwin Kepner; Weiss, Scott Tillman (BioMed Central, 2010)
      Background: Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using ...

    • Comparison of Linkage and Association Strategies for Quantitative Traits Using the COGA Dataset 

      McQueen, Matthew B; Murphy, Amy; Kraft, Peter; Su, Jessica Ann Lasky; Lazarus, Ross; Laird, Nan M.; Lange, Christoph; Van Steen, Kristel (BioMed Central, 2005)
      Genome scans using dense single-nucleotide polymorphism (SNP) data have recently become a reality. It is thought that the increase in information content for linkage analysis as a result of the denser scans will help refine ...

    • Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3 

      Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E. (2015)
      The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). ...

    • A general semi-parametric approach to the analysis of genetic association studies in population-based designs 

      Lutz, Sharon; Yip, Wai-Ki; Hokanson, John; Laird, Nan M.; Lange, Christoph (BioMed Central, 2013)
      Background: For genetic association studies in designs of unrelated individuals, current statistical methodology typically models the phenotype of interest as a function of the genotype and assumes a known statistical model ...

    • A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry 

      Lutz, Sharon M.; Cho, Michael H.; Young, Kendra; Hersh, Craig P.; Castaldi, Peter J.; McDonald, Merry-Lynn; Regan, Elizabeth; Mattheisen, Manuel; DeMeo, Dawn L.; Parker, Margaret; Foreman, Marilyn; Make, Barry J.; Jensen, Robert L.; Casaburi, Richard; Lomas, David A.; Bhatt, Surya P.; Bakke, Per; Gulsvik, Amund; Crapo, James D.; Beaty, Terri H.; Laird, Nan M.; Lange, Christoph; Hokanson, John E.; Silverman, Edwin K. (BioMed Central, 2015)
      Background: Pulmonary function decline is a major contributor to morbidity and mortality among smokers. Post bronchodilator FEV1 and FEV1/FVC ratio are considered the standard assessment of airflow obstruction. We performed ...

    • A genome-wide association study of bronchodilator response in asthmatics 

      Duan, Q; Lasky-Su, Jessica A. Lasky; Himes, Blanca; Qiu, Weiliang; Litonjua, Augusto Ampil; Damask, Amy; Lazarus, Richard James; Klanderman, Barbara; Irvin, Charles G.; Peters, Stephen P; Hanrahan, John P; Lima, John J.; Martinez, Fernando D.; Mauger, David; Chinchilli, Vernon M.; Soto-Quiros, Manuel; Avila, Lydiana; Celedón, Juan C.; Lange, Christoph; Weiss, Scott Tillman; Tantisira, Kelan (Nature Publishing Group, 2013)
      Reversibility of airway obstruction in response to β2-agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) ...

    • Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma 

      Tantisira, Kelan; Lasky-Su, Jessica A. Lasky; Harada, Michishige; Murphy, Amy; Litonjua, Augusto Ampil; Himes, Blanca; Lange, Christoph; Lazarus, Ross; Sylvia, Jody; Klanderman, Barbara; Duan, Qing Ling; Qiu, Weiliang; Hirota, Tomomitsu; Martinez, Fernando D.; Mauger, David; Sorkness, Christine; Szefler, Stanley; Lazarus, Stephen C.; Lemanske, Robert F.; Peters, Stephen P.; Lima, John J.; Nakamura, Yusuke; Tamari, Mayumi; Weiss, Scott Tillman (New England Journal of Medicine (NEJM/MMS), 2011)
      Background: The response to treatment for asthma is characterized by wide interindividual variability, with a significant number of patients who have no response. We hypothesized that a genomewide association study would ...

    • Genomic Screening in Family-Based Association Testing 

      Murphy, Amy; McQueen, Matthew B; Su, Jessica Ann Lasky; Kraft, Peter; Lazarus, Ross; Laird, Nan M.; Lange, Christoph; Van Steen, Kristel (BioMed Central, 2005)
      Due to the recent gains in the availability of single-nucleotide polymorphism data, genome-wide association testing has become feasible. It is hoped that this additional data may confirm the presence of disease susceptibility ...

    • Handling the data management needs of high-throughput sequencing data: SpeedGene, a compression algorithm for the efficient storage of genetic data 

      Qiao, Dandi; Yip, Wai-Ki; Lange, Christoph (BioMed Central, 2012)
      Background: As Next-Generation Sequencing data becomes available, existing hardware environments do not provide sufficient storage space and computational power to store and process the data due to their enormous size. ...

    • Hypothesis Testing in GWAS and Statistical Issues with Compensation in Clinical Trials 

      Swanson, David Michael (2013-09-27)
      We first show theoretically and in simulation how power varies as a function of SNP correlation structure with currently-implemented gene-based testing methods. We propose alternative testing methods whose power does not ...

    • Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia 

      Juraeva, Dilafruz; Haenisch, Britta; Zapatka, Marc; Frank, Josef; Witt, Stephanie H.; Mühleisen, Thomas W.; Treutlein, Jens; Strohmaier, Jana; Meier, Sandra; Degenhardt, Franziska; Giegling, Ina; Ripke, Stephan; Leber, Markus; Lange, Christoph; Schulze, Thomas G.; Mössner, Rainald; Nenadic, Igor; Sauer, Heinrich; Rujescu, Dan; Maier, Wolfgang; Børglum, Anders; Ophoff, Roel; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella; Mattheisen, Manuel; Brors, Benedikt (Public Library of Science, 2014)
      In the present study, an integrated hierarchical approach was applied to: (1) identify pathways associated with susceptibility to schizophrenia; (2) detect genes that may be potentially affected in these pathways since ...

    • ‘Location, Location, Location’: a spatial approach for rare variant analysis and an application to a study on non-syndromic cleft lip with or without cleft palate 

      Fier, Heide; Won, Sungho; Prokopenko, Dmitry; AlChawa, Taofik; Ludwig, Kerstin U.; Fimmers, Rolf; Silverman, Edwin K.; Pagano, Marcello; Mangold, Elisabeth; Lange, Christoph (Oxford University Press, 2012)
      Motivation: For the analysis of rare variants in sequence data, numerous approaches have been suggested. Fixed and flexible threshold approaches collapse the rare variant information of a genomic region into a test statistic ...

    • Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design? 

      Heid, Iris M.; Huth, Cornelia; Loos, Ruth J. F.; Kronenberg, Florian; Adamkova, Vera; Anand, Sonia S.; Ardlie, Kristin; Biebermann, Heike; Bjerregaard, Peter; Boeing, Heiner; Bouchard, Claude; Ciullo, Marina; Cooper, Jackie A.; Corella, Dolores; Dina, Christian; Engert, James C.; Fisher, Eva; Francès, Francesc; Froguel, Philippe; Hebebrand, Johannes; Hegele, Robert A.; Hinney, Anke; Hoehe, Margret R.; Hubacek, Jaroslav A.; Humphries, Steve E.; Hunt, Steven C.; Illig, Thomas; Järvelin, Marjo-Riita; Kaakinen, Marika; Kollerits, Barbara; Krude, Heiko; Kumar, Jitender; Lange, Leslie A.; Langer, Birgit; Li, Shengxu; Luchner, Andreas; Meyre, David; Mohlke, Karen L.; Mooser, Vincent; Nebel, Almut; Nguyen, Thuy Trang; Paulweber, Bernhard; Perusse, Louis; Rankinen, Tuomo; Rosskopf, Dieter; Schreiber, Stefan; Sengupta, Shantanu; Sorice, Rossella; Suk, Anita; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Völzke, Henry; Vimaleswaran, Karani S.; Wareham, Nicholas J.; Waterworth, Dawn; Yusuf, Salim; Lindgren, Cecilia; McCarthy, Mark I.; Wichmann, H.-Erich; Allison, David B.; Hu, Frank B.; Qi, Lu; Lyon, Helen N; Lange, Christoph; Hirschhorn, Joel Naom; Laird, Nan M. (Public Library of Science, 2009)
      The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), ...

    • On Quality Control Measures in Genome-wide Association Studies: A Test to Assess the Genotyping Quality of Individual Probands in Family-based Association Studies and an Application to the HapMap Data 

      Fardo, David W.; Ionita-Laza, Iuliana; Dermitzakis, Emmanouil T.; Lange, Christoph (Public Library of Science, 2009)
      Allele transmissions in pedigrees provide a natural way of evaluating the genotyping quality of a particular proband in a family-based, genome-wide association study. We propose a transmission test that is based on this ...

    • On the Analysis of Genome-Wide Association Studies in Family-Based Designs: A Universal, Robust Analysis Approach and an Application to Four Genome-Wide Association Studies 

      Won, Sungho; Wilk, Jemma B; Mathias, Rasika A.; O'Donnell, Christopher Joseph; Silverman, Edwin Kepner; Barnes, Kathleen; O'Connor, George T.; Weiss, Scott Tillman; Lange, Christoph (Public Library of Science, 2009)
      For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, ...

    • On the Recombination Rate Estimation in the Presence of Population Substructure 

      Hecker, Julian; Prokopenko, Dmitry; Lange, Christoph; Fier, Heide Löhlein (Public Library of Science, 2015)
      As recombination events are not uniformly distributed along the human genome, the estimation of fine-scale recombination maps, e.g. HapMap Project, has been one of the major research endeavors over the last couple of years. ...

    • PBAT: A comprehensive software package for genome-wide association analysis of complex family-based studies 

      Van Steen, Kristel; Lange, Christoph (BioMed Central, 2005)
      The PBAT software package (v2.5) provides a unique set of tools for complex family-based association analysis at a genome-wide level. PBAT can handle nuclear families with missing parental genotypes, extended pedigrees ...