Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls
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{"title"=>"Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls", "type"=>"journal", "authors"=>[{"first_name"=>"Li", "last_name"=>"Liu", "scopus_author_id"=>"56544764000"}, {"first_name"=>"Aniko", "last_name"=>"Sabo", "scopus_author_id"=>"7007098534"}, {"first_name"=>"Benjamin M.", "last_name"=>"Neale", "scopus_author_id"=>"55331817400"}, {"first_name"=>"Uma", "last_name"=>"Nagaswamy", "scopus_author_id"=>"6507500836"}, {"first_name"=>"Christine", "last_name"=>"Stevens", "scopus_author_id"=>"24178358100"}, {"first_name"=>"Elaine", "last_name"=>"Lim", "scopus_author_id"=>"55177996200"}, {"first_name"=>"Corneliu A.", "last_name"=>"Bodea", "scopus_author_id"=>"57114942200"}, {"first_name"=>"Donna", "last_name"=>"Muzny", "scopus_author_id"=>"6603763638"}, {"first_name"=>"Jeffrey G.", "last_name"=>"Reid", "scopus_author_id"=>"15048598500"}, {"first_name"=>"Eric", "last_name"=>"Banks", "scopus_author_id"=>"36514157400"}, {"first_name"=>"Hillary", "last_name"=>"Coon", "scopus_author_id"=>"7005857533"}, {"first_name"=>"Mark", "last_name"=>"DePristo", "scopus_author_id"=>"6602278308"}, {"first_name"=>"Huyen", "last_name"=>"Dinh", "scopus_author_id"=>"8305228300"}, {"first_name"=>"Tim", "last_name"=>"Fennel", "scopus_author_id"=>"55669398800"}, {"first_name"=>"Jason", "last_name"=>"Flannick", "scopus_author_id"=>"8719247900"}, {"first_name"=>"Stacey", "last_name"=>"Gabriel", "scopus_author_id"=>"7202104113"}, {"first_name"=>"Kiran", "last_name"=>"Garimella", "scopus_author_id"=>"36514651600"}, {"first_name"=>"Shannon", "last_name"=>"Gross", "scopus_author_id"=>"37012467400"}, {"first_name"=>"Alicia", "last_name"=>"Hawes", "scopus_author_id"=>"7004480618"}, {"first_name"=>"Lora", "last_name"=>"Lewis", "scopus_author_id"=>"35353938300"}, {"first_name"=>"Vladimir", "last_name"=>"Makarov", "scopus_author_id"=>"55871121994"}, {"first_name"=>"Jared", "last_name"=>"Maguire", "scopus_author_id"=>"26027944100"}, {"first_name"=>"Irene", "last_name"=>"Newsham", "scopus_author_id"=>"7003449917"}, {"first_name"=>"Ryan", "last_name"=>"Poplin", "scopus_author_id"=>"37026985800"}, {"first_name"=>"Stephan", "last_name"=>"Ripke", "scopus_author_id"=>"23398729000"}, {"first_name"=>"Khalid", "last_name"=>"Shakir", "scopus_author_id"=>"43161386000"}, {"first_name"=>"Kaitlin E.", "last_name"=>"Samocha", "scopus_author_id"=>"57196325565"}, {"first_name"=>"Yuanqing", "last_name"=>"Wu", "scopus_author_id"=>"7406891685"}, {"first_name"=>"Eric", "last_name"=>"Boerwinkle", "scopus_author_id"=>"7102087489"}, {"first_name"=>"Joseph D.", "last_name"=>"Buxbaum", "scopus_author_id"=>"26643309400"}, {"first_name"=>"Edwin H.", "last_name"=>"Cook", "scopus_author_id"=>"7202259523"}, {"first_name"=>"Bernie", "last_name"=>"Devlin", "scopus_author_id"=>"35351356600"}, {"first_name"=>"Gerard D.", "last_name"=>"Schellenberg", "scopus_author_id"=>"35371216000"}, {"first_name"=>"James S.", "last_name"=>"Sutcliffe", "scopus_author_id"=>"7101638712"}, {"first_name"=>"Mark J.", "last_name"=>"Daly", "scopus_author_id"=>"7201456226"}, {"first_name"=>"Richard A.", "last_name"=>"Gibbs", "scopus_author_id"=>"7202068919"}, {"first_name"=>"Kathryn", "last_name"=>"Roeder", "scopus_author_id"=>"7103005216"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"368819471", "issn"=>"15537390", "isbn"=>"1553-7404", "doi"=>"10.1371/journal.pgen.1003443", "scopus"=>"2-s2.0-84876852800", "pmid"=>"23593035", "sgr"=>"84876852800"}, "id"=>"a32896fc-e968-3394-8d80-38d4f5a583e7", "abstract"=>"We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD.", "link"=>"http://www.mendeley.com/research/analysis-rare-exonic-variation-amongst-subjects-autism-spectrum-disorders-population-controls-1", "reader_count"=>137, "reader_count_by_academic_status"=>{"Unspecified"=>6, "Professor > Associate Professor"=>10, "Librarian"=>1, "Researcher"=>37, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>37, "Student > Postgraduate"=>8, "Student > Master"=>13, "Other"=>5, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>9}, "reader_count_by_user_role"=>{"Unspecified"=>6, "Professor > Associate Professor"=>10, "Librarian"=>1, "Researcher"=>37, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>37, "Student > Postgraduate"=>8, "Student > Master"=>13, "Other"=>5, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>9}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Biochemistry, Genetics and Molecular Biology"=>21, "Mathematics"=>2, "Medicine and Dentistry"=>17, "Agricultural and Biological Sciences"=>68, "Neuroscience"=>7, "Arts and Humanities"=>1, "Psychology"=>4, "Social Sciences"=>3, "Computer Science"=>4, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>17}, "Neuroscience"=>{"Neuroscience"=>7}, "Social Sciences"=>{"Social Sciences"=>3}, "Psychology"=>{"Psychology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>68}, "Computer Science"=>{"Computer Science"=>4}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>21}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>8}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Netherlands"=>2, "Hong Kong"=>1, "United States"=>5, "Luxembourg"=>1, "Brazil"=>2, "United Kingdom"=>4, "Mexico"=>1, "Iceland"=>1, "Germany"=>1}, "group_count"=>12}

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  • {"files"=>["https://ndownloader.figshare.com/files/1022157"], "description"=>"<p>Minor allele counts (MAC) are restricted to variants with minor allele frequency . Panel (A), distribution of mean MAC per sample, averaged over all genes. Panel (B), in the Baylor samples, genes were binned based on the counts of rare variants (which range from 1 to 30); for each bin the vertical axis shows the distribution of counts (boxplot) from the same genes in the Broad samples. The red line indicates an equal count in Broad and Baylor.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "variants", "baylor", "sets"], "article_id"=>680626, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_rare_variants_per_gene_in_Baylor_and_Broad_data_sets_after_filtering_/680626", "title"=>"Distribution of rare variants per gene in Baylor and Broad data sets after filtering.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022158"], "description"=>"<p>Theoretical power functions of meta- (red) and mega-analysis (blue) at significance level of . is the strength of signal per variant and is the number of rare variants. (A) ; (B) ; (C) ; and (D) .</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "meta"], "article_id"=>680627, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Theoretical_power_comparison_Meta_versus_Mega_/680627", "title"=>"Theoretical power comparison: Meta versus Mega.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022159"], "description"=>"<p>The empirical power comparisons of SKAT applied to Broad (blue), Baylor (green), and combined via mega- (red) and meta-analysis (orange). We use causal variants to generate the phenotype based on the model in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003443#pgen.1003443.e124\" target=\"_blank\">Eqn. 1</a> with . Causal rate is the fraction of variants with , which varied from 20% to 50%. We choose weights and use SKAT to calculate the p-values for Baylor, Broad and merged data sets. We combine all singleton variants as a super-variant. For meta analysis, the weighted Z-score method combines the two p-values from Baylor and Broad for each gene. Panel (A) and the significance level is set at .001; in panel (B) and the significance level is set at .01.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics"], "article_id"=>680628, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulation_of_power_/680628", "title"=>"Simulation of power.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022160"], "description"=>"<p>144 genes are selected from the Broad data set. Each gene has exactly rare variants, . For each gene, we first randomly assign the phenotypes for 913 samples based on a coin toss, then calculate the test statistics , and corresponding p-value computed under the assumption that . We repeat this 100 times per gene, to obtain more than 10,000 p-values.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "simulation", "linkage", "disequilibrium", "variants"], "article_id"=>680629, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Q_8211_Q_plot_of_simulation_tests_under_the_assumption_that_linkage_disequilibrium_among_rare_variants_has_little_impact_on_the_distribution_of_the_test_statistic_/680629", "title"=>"Q–Q plot of simulation tests under the assumption that linkage disequilibrium among rare variants has little impact on the distribution of the test statistic.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022161"], "description"=>"<p>Plotted are the first eigen-vector versus second eigen-vector for Broad samples. Eigen-vectors are obtained by applying PCA to all common variants that have no missingness (56,607 variants) (A), all low frequency variants that have no missingness (29,509 variants) (B), and both type of variants (C). The colors are obtained by clustering individuals based on their coordinates in panel (A) using model based clustering <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003443#pgen.1003443-Fraley1\" target=\"_blank\">[51]</a>.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "types"], "article_id"=>680630, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PCA_from_common_variants_low_frequency_variants_and_both_types_of_variants_/680630", "title"=>"PCA from common variants, low frequency variants, and both types of variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022162"], "description"=>"<p>Panels (A) and (B) plot the top two eigen-vectors for Baylor and Broad, respectively. Eigen-vectors are obtained by applying PCA to all common variants (CVs) that have no missingness (14,702 CVs used in Baylor and 56,607 CVs used in Broad).</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics"], "article_id"=>680631, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PCA_for_case_orange_and_control_blue_samples_/680631", "title"=>"PCA for case (orange) and control (blue) samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022164"], "description"=>"<p>The first eigen-vector versus second eigen-vector for (A) Baylor and (B) Broad samples. Eigen-vectors are obtained by applying PCA to all common variants. For each individual, we count the number of doubletons. To indicate the relative number of doubletons per individual, points are color-coded as follows: black (bottom : fewest doubletons), blue (next 25), green (next 25), and orange (top 25: most doubletons) within the Baylor and Broad samples, respectively.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "doubletons"], "article_id"=>680633, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_doubletons_as_a_function_of_the_eigen_map_/680633", "title"=>"Distribution of doubletons as a function of the eigen-map.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022165"], "description"=>"<p>MAC_c are computed for all variants with minor allele frequency . Panel (A) is the doubleton counts of Baylor cases versus MACs of CVs in the exome. Panel (B) is a zoomed in version of panel (A). Panel (C) is the doubleton counts of Broad cases versus MAC_c of CVs in the exome.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "counts", "allele", "variants"], "article_id"=>680634, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Doubletons_counts_versus_minor_allele_counts_MAC_c_in_common_variants_CVs_/680634", "title"=>"Doubletons counts versus minor allele counts (MAC_c) in common variants (CVs).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022166"], "description"=>"<p>By permuting case/control status 100 times the distribution of is obtained based on the 1000 largest genes. The red line shows the mean of the permutation distribution and the green line shows obtained from the data using (A) Broad SKAT p-values obtained without eigen-vectors; (B) Broad SKAT p-values, with common variants (CVs) eigen-vectors, (C) Broad SKAT p-values, with low frequency variants (LFVs) eigen-vectors; and (D) Broad SKAT p-values, with CVs plus LFVs eigen-vectors.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "genomic"], "article_id"=>680635, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_the_genomic_control_factor_/680635", "title"=>"Distribution of the genomic control factor .", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022167"], "description"=>"<p>Panel (A) shows SKAT p-values, Panel (B) shows burden test p-values. and 1.047, for mega SKAT and burden test, respectively.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "skat"], "article_id"=>680636, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_log10_observed_p_values_versus_log10_expected_p_values_of_SKAT_and_Burden_test_for_Mega_analysis_/680636", "title"=>"-log10(observed p-values) versus -log10(expected p-values) of SKAT and Burden test for Mega-analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-11 00:10:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022168"], "description"=>"<p>Note: These analyses are for all non-synonymous variants with MAF.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "missingness"], "article_id"=>680637, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Counts_of_missingness_per_sample_after_filtering_/680637", "title"=>"Counts of missingness per sample after filtering.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-11 00:10:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022169"], "description"=>"<p>Note: These analyses are restricted to the genes that have more than 15 minor alleles in the samples used in each study. MAC columns show the number of minor alleles called per sample, Ba: Baylor, Br: Broad. Filter PASS includes all variants that score a “Pass” based on GATK, Filter MISS: missingness , Filter DpBal: missingness , depth balance for Baylor, for Broad.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "genes"], "article_id"=>680638, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_significant_genes_and_expected_number_under_different_filters_/680638", "title"=>"Number of significant genes (and expected number) under different filters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-11 00:10:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022170"], "description"=>"<p>Note: These analyses are restricted to the genes that have more than 4 minor alleles in the samples used in each study. and are calculated based on the median and the 1st quantile of the p-value distribution, respectively. PC adjustment is based on the common variants (CVs) eigen-vectors.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "pc"], "article_id"=>680639, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genomic_control_and_for_all_tests_before_and_after_PC_adjustment_/680639", "title"=>"Genomic control and for all tests before and after PC adjustment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-11 00:10:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022171"], "description"=>"<p>Note: Single: count of singletons; Double: count of doubletons; RVs: count of variants with MAF and not singletons or doubletons; LFVs: count of variants with MAF ; CVs: count of variants with MAF .</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "non-synonymous", "variants", "baylor"], "article_id"=>680640, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.t005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Counts_of_non_synonymous_variants_in_Baylor_and_Broad_before_filtering_/680640", "title"=>"Counts of non-synonymous variants in Baylor and Broad before filtering.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-11 00:10:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022172"], "description"=>"<p>Note: Significance level is 0.01, not corrected for muliple testing. The analyses of the first two rows are for all genes that have at least one MAC in Baylor and Broad dataset. The last rows are restricted to the genes that have more than 15 minor alleles after combining Baylor and Broad datasets.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "nominally", "genes"], "article_id"=>680641, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.t004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_nominally_significant_genes_before_and_after_filtering_/680641", "title"=>"Number of nominally significant genes before and after filtering.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-04-11 00:10:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/1022173", "https://ndownloader.figshare.com/files/1022174", "https://ndownloader.figshare.com/files/1022175", "https://ndownloader.figshare.com/files/1022176", "https://ndownloader.figshare.com/files/1022177", "https://ndownloader.figshare.com/files/1022178", "https://ndownloader.figshare.com/files/1022179", "https://ndownloader.figshare.com/files/1022180", "https://ndownloader.figshare.com/files/1022181", "https://ndownloader.figshare.com/files/1022182", "https://ndownloader.figshare.com/files/1022183", "https://ndownloader.figshare.com/files/1022184", "https://ndownloader.figshare.com/files/1022185", "https://ndownloader.figshare.com/files/1022186", "https://ndownloader.figshare.com/files/1022187"], "description"=>"<div><p>We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD.</p></div>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "statistics", "exonic", "amongst", "subjects", "autism", "disorders"], "article_id"=>680642, "categories"=>["Mathematics", "Biological Sciences"], "users"=>["Li Liu", "Aniko Sabo", "Benjamin M. Neale", "Uma Nagaswamy", "Christine Stevens", "Elaine Lim", "Corneliu A. Bodea", "Donna Muzny", "Jeffrey G. Reid", "Eric Banks", "Hillary Coon", "Mark DePristo", "Huyen Dinh", "Tim Fennel", "Jason Flannick", "Stacey Gabriel", "Kiran Garimella", "Shannon Gross", "Alicia Hawes", "Lora Lewis", "Vladimir Makarov", "Jared Maguire", "Irene Newsham", "Ryan Poplin", "Stephan Ripke", "Khalid Shakir", "Kaitlin E. Samocha", "Yuanqing Wu", "Eric Boerwinkle", "Joseph D. Buxbaum", "Edwin H. Cook Jr", "Bernie Devlin", "Gerard D. Schellenberg", "James S. Sutcliffe", "Mark J. Daly", "Richard A. Gibbs", "Kathryn Roeder"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003443.s001", "https://dx.doi.org/10.1371/journal.pgen.1003443.s002", "https://dx.doi.org/10.1371/journal.pgen.1003443.s003", "https://dx.doi.org/10.1371/journal.pgen.1003443.s004", "https://dx.doi.org/10.1371/journal.pgen.1003443.s005", "https://dx.doi.org/10.1371/journal.pgen.1003443.s006", "https://dx.doi.org/10.1371/journal.pgen.1003443.s007", "https://dx.doi.org/10.1371/journal.pgen.1003443.s008", "https://dx.doi.org/10.1371/journal.pgen.1003443.s009", "https://dx.doi.org/10.1371/journal.pgen.1003443.s010", "https://dx.doi.org/10.1371/journal.pgen.1003443.s011", "https://dx.doi.org/10.1371/journal.pgen.1003443.s012", "https://dx.doi.org/10.1371/journal.pgen.1003443.s013", "https://dx.doi.org/10.1371/journal.pgen.1003443.s014", "https://dx.doi.org/10.1371/journal.pgen.1003443.s015"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_Rare_Exonic_Variation_amongst_Subjects_with_Autism_Spectrum_Disorders_and_Population_Controls_/680642", "title"=>"Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-04-11 00:10:42"}

PMC Usage Stats | Further Information

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Relative Metric

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