Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics
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{"title"=>"Measures of autozygosity in decline: Globalization, urbanization, and its implications for medical genetics", "type"=>"journal", "authors"=>[{"first_name"=>"Michael A.", "last_name"=>"Nalls", "scopus_author_id"=>"55630773200"}, {"first_name"=>"Javier", "last_name"=>"Simon-Sanchez", "scopus_author_id"=>"8509226500"}, {"first_name"=>"J. Raphael", "last_name"=>"Gibbs", "scopus_author_id"=>"16028171700"}, {"first_name"=>"Coro", "last_name"=>"Paisan-Ruiz", "scopus_author_id"=>"15123039100"}, {"first_name"=>"Jose Tomas", "last_name"=>"Bras", "scopus_author_id"=>"57200436456"}, {"first_name"=>"Toshiko", "last_name"=>"Tanaka", "scopus_author_id"=>"35273742500"}, {"first_name"=>"Mar", "last_name"=>"Matarin", "scopus_author_id"=>"23492858300"}, {"first_name"=>"Sonja", "last_name"=>"Scholz", "scopus_author_id"=>"12240193500"}, {"first_name"=>"Charles", "last_name"=>"Weitz", "scopus_author_id"=>"7003364206"}, {"first_name"=>"Tamara B.", "last_name"=>"Harris", "scopus_author_id"=>"35375662400"}, {"first_name"=>"Luigi", "last_name"=>"Ferrucci", "scopus_author_id"=>"55239601400"}, {"first_name"=>"John", "last_name"=>"Hardy", "scopus_author_id"=>"56210513900"}, {"first_name"=>"Andrew B.", "last_name"=>"Singleton", "scopus_author_id"=>"7006092717"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"63449140483", "pmid"=>"19282984", "isbn"=>"1553-7404 (Electronic)", "scopus"=>"2-s2.0-63449140483", "issn"=>"15537390", "pui"=>"354404877", "doi"=>"10.1371/journal.pgen.1000415"}, "id"=>"58c3b9d3-8c64-3f5c-8493-301310d53a7b", "abstract"=>"This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19-99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so.", "link"=>"http://www.mendeley.com/research/measures-autozygosity-decline-globalization-urbanization-implications-medical-genetics", "reader_count"=>64, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>29, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>3, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>29, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>3, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Lecturer > Senior Lecturer"=>3, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>42, "Medicine and Dentistry"=>11, "Arts and Humanities"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>1, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>42}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>2}}, "reader_count_by_country"=>{"Canada"=>1, "Austria"=>1, "Afghanistan"=>1, "United States"=>4, "Poland"=>1, "United Kingdom"=>4, "Germany"=>1}, "group_count"=>5}

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  • {"files"=>["https://ndownloader.figshare.com/files/447652", "https://ndownloader.figshare.com/files/447681", "https://ndownloader.figshare.com/files/447726"], "description"=>"<div><p>This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19–99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, <em>p</em><0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so.</p></div>", "links"=>[], "tags"=>["measures", "autozygosity", "implications", "genetics"], "article_id"=>148224, "categories"=>["Genetics"], "users"=>["Michael A. Nalls", "Javier Simón-Sánchez", "J. Raphael Gibbs", "Coro Paisan-Ruiz", "Jose Tomas Bras", "Toshiko Tanaka", "Mar Matarin", "Sonja Scholz", "Charles Weitz", "Tamara B. Harris", "Luigi Ferrucci", "John Hardy", "Andrew B. Singleton"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000415.s001", "https://dx.doi.org/10.1371/journal.pgen.1000415.s002", "https://dx.doi.org/10.1371/journal.pgen.1000415.s003"], "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Measures_of_Autozygosity_in_Decline_Globalization_Urbanization_and_Its_Implications_for_Medical_Genetics/148224", "title"=>"Measures of Autozygosity in Decline: Globalization, Urbanization, and Its Implications for Medical Genetics", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-03-13 02:17:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/905465"], "description"=>"<p>Model 1 is unadjusted.</p><p>Model 2 includes covariate of observed homozygosity outside of LD.</p><p>Model 3 includes covariate of expected homozygosity outside of LD.</p><p>Model 4 includes covariate of F<sub>ld</sub> for dependent variables of number of ROHs, %ROH and average ROH length, for the models using F<sub>ld</sub> as the dependent variable average ROH length was used as a covariate.</p>", "links"=>[], "tags"=>["regression", "models", "autozygosity", "measures", "positively", "correlated", "chronological", "standardized", "coefficients"], "article_id"=>575901, "categories"=>["Genetics"], "users"=>["Michael A. Nalls", "Javier Simón-Sánchez", "J. Raphael Gibbs", "Coro Paisan-Ruiz", "Jose Tomas Bras", "Toshiko Tanaka", "Mar Matarin", "Sonja Scholz", "Charles Weitz", "Tamara B. Harris", "Luigi Ferrucci", "John Hardy", "Andrew B. Singleton"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000415.t003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linear_regression_models_showing_autozygosity_measures_are_positively_correlated_with_chronological_age_standardized_to_2008_reporting_standardized_946_coefficients_and_p_values_/575901", "title"=>"Linear regression models showing autozygosity measures are positively correlated with chronological age (standardized to 2008), reporting standardized β coefficients and p-values.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-13 01:38:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/905333"], "description"=>"<p>Estimates of trends for declining autozygosity in individuals born in the twentieth century. These predictive models include decreasing (A) %ROH, (B) number of ROHs, (C) F<sub>ld</sub> and the (D) average length of ROHs. The black lines represents linear predictive trends, and the grey shaded area represents the 95% confidence interval for these estimates.</p>", "links"=>[], "tags"=>["predictive", "models", "declining", "measures", "autozygosity"], "article_id"=>575774, "categories"=>["Genetics"], "users"=>["Michael A. Nalls", "Javier Simón-Sánchez", "J. Raphael Gibbs", "Coro Paisan-Ruiz", "Jose Tomas Bras", "Toshiko Tanaka", "Mar Matarin", "Sonja Scholz", "Charles Weitz", "Tamara B. Harris", "Luigi Ferrucci", "John Hardy", "Andrew B. Singleton"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000415.g001", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linear_predictive_models_show_declining_measures_of_autozygosity_and_F_ld_/575774", "title"=>"Linear predictive models show declining measures of autozygosity and F<sub>ld</sub>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-13 01:36:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/905520"], "description"=>"<p>All measures in mean (standard deviation) format when applicable.</p>*<p>indicates significant difference of within row-comparison of measures in Coriell samples (p-value<0.05).</p>$<p>indicates significant difference within row-comparison of measures in BLSA samples (p-value<0.05).</p>x<p>indicates suggestive (p-value<0.07).</p>", "links"=>[], "tags"=>["autozygosity", "20-year"], "article_id"=>575961, "categories"=>["Genetics"], "users"=>["Michael A. Nalls", "Javier Simón-Sánchez", "J. Raphael Gibbs", "Coro Paisan-Ruiz", "Jose Tomas Bras", "Toshiko Tanaka", "Mar Matarin", "Sonja Scholz", "Charles Weitz", "Tamara B. Harris", "Luigi Ferrucci", "John Hardy", "Andrew B. Singleton"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000415.t002", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Measures_of_autozygosity_vary_by_20_year_age_groups_/575961", "title"=>"Measures of autozygosity vary by 20-year age groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-13 01:39:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/905569"], "description"=>"<p>All measures in mean (standard deviation).</p>", "links"=>[], "tags"=>["genetics and genomics", "genetics and genomics/bioinformatics", "genetics and genomics/medical genetics", "genetics and genomics/population genetics"], "article_id"=>576015, "categories"=>["Genetics"], "users"=>["Michael A. Nalls", "Javier Simón-Sánchez", "J. Raphael Gibbs", "Coro Paisan-Ruiz", "Jose Tomas Bras", "Toshiko Tanaka", "Mar Matarin", "Sonja Scholz", "Charles Weitz", "Tamara B. Harris", "Luigi Ferrucci", "John Hardy", "Andrew B. Singleton"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000415.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Descriptive_statistics_for_total_population_/576015", "title"=>"Descriptive statistics for total population.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2009-03-13 01:40:15"}

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