title: FARVAT: a family-based rare variant association test.
abstract: BACKGROUND
  Individuals in each family are genetically more homogeneous than unrelated individuals, and family-based designs are often recommended for the analysis of rare variants. However, despite the importance of family-based samples analysis, few statistical methods for rare variant association analysis are available.
  
  
  RESULTS
  In this report, we propose a FAmily-based Rare Variant Association Test (FARVAT). FARVAT is based on the quasi-likelihood of whole families, and is statistically and computationally efficient for the extended families. FARVAT assumed that families were ascertained with the disease status of family members, and incorporation of the estimated genetic relationship matrix to the proposed method provided robustness under the presence of the population substructure. Depending on the choice of working matrix, our method could be a burden test or a variance component test, and could be extended to the SKAT-O-type statistic. FARVAT was implemented in C++, and application of the proposed method to schizophrenia data and simulated data for GAW17 illustrated its practical importance.
  
  
  BACKGROUND
  The software calculates various statistics for the analysis of related samples, and it is freely downloadable from http://healthstats.snu.ac.kr/software/farvat.
  
  
  BACKGROUND
  won1@snu.ac.kr or tspark@stats.snu.ac.kr
  
  
  BACKGROUND
  supplementary data are available at Bioinformatics online.
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Sungkyoung
authors: S
authors: Choi
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Sungyoung
authors: S
authors: Lee
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Sven
authors: S
authors: Cichon
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Markus M
authors: MM
authors: Nöthen
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Christoph
authors: C
authors: Lange
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Taesung
authors: T
authors: Park
authors: Interdisciplinary Program in bioinformatics, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea, Institute of Human Genetics, University of Bonn, D-53127 Bonn, Germany, Department of Biostatistics, Harvard School of Public Health, 677 Huntington Avenue. Boston, MA 02115, USA, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA, Center for Genomic Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA, Department of Biostatistics, Harvard School of Public Health, 667 Huntington Ave, Boston, MA 02115, USA, Institute for Genomic Mathematics, University of Bonn, D-53127 Bonn, Germany, German Center for Neurodegenerative Diseases, D-53127 Bonn, Germany, Department of Statistics, Seoul National University 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea and Department of Public Health Science, Seoul National University, 1 Kwanak-ro Kwanak-gu, Seoul 151-742, Korea.
authors: Sungho
authors: S
authors: Won
mesh_terms: D005190:Family; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D012559:Schizophrenia / Q000235:genetics; D012984:Software