Positive Selection on Loci Associated with Drug and Alcohol Dependence
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{"title"=>"Positive selection on loci associated with drug and alcohol dependence", "type"=>"journal", "authors"=>[{"first_name"=>"Brooke", "last_name"=>"Sadler", "scopus_author_id"=>"55163406800"}, {"first_name"=>"Gabe", "last_name"=>"Haller", "scopus_author_id"=>"35198064200"}, {"first_name"=>"Howard", "last_name"=>"Edenberg", "scopus_author_id"=>"7006853081"}, {"first_name"=>"Jay", "last_name"=>"Tischfield", "scopus_author_id"=>"7004449404"}, {"first_name"=>"Andy", "last_name"=>"Brooks", "scopus_author_id"=>"7202570520"}, {"first_name"=>"John", "last_name"=>"Kramer", "scopus_author_id"=>"55729093800"}, {"first_name"=>"Marc", "last_name"=>"Schuckit", "scopus_author_id"=>"35402912400"}, {"first_name"=>"John", "last_name"=>"Nurnberger", "scopus_author_id"=>"35353542700"}, {"first_name"=>"Alison", "last_name"=>"Goate", "scopus_author_id"=>"7006308333"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84942937633", "doi"=>"10.1371/journal.pone.0134393", "pmid"=>"26270548", "issn"=>"19326203", "scopus"=>"2-s2.0-84942937633", "pui"=>"606194931"}, "id"=>"cce7e651-75a3-397c-acc4-6c7c133f21a9", "abstract"=>"Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.", "link"=>"http://www.mendeley.com/research/positive-selection-loci-associated-drug-alcohol-dependence", "reader_count"=>13, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>3, "Neuroscience"=>2}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2211741"], "description"=>"<p>All SNPs have r<sup>2</sup> value of 0.8 or greater with rs1451240. Significant values and SNP names are bolded.</p><p>Tajima’s D and iHS values for <i>CHRNB3-CHRNA6</i> region.</p>", "links"=>[], "tags"=>["cocaine dependence", "coga", "Collaborative Studies", "WAIS Digit Symbol", "Loci Associated", "nicotine dependence", "Wechsler Adult Intelligence Scale", "17 SNPs genotyped", "region", "use 1000 Genomes sequence data", "WAIS Information tests", "CHRNA 5 nicotinic receptor gene", "nicotinic receptor gene clusters", "block design", "WAIS digit symbol test results", "evidence selection", "Positive Selection", "reaction time", "test variants", "nicotinic receptor gene cluster", "3 populations", "alcohol dependence", "phenotype", "haplotype score", "chromosomes 8", "Nicotine addiction", "Several loci"], "article_id"=>1510437, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Brooke Sadler", "Gabe Haller", "Howard Edenberg", "Jay Tischfield", "Andy Brooks", "John Kramer", "Marc Schuckit", "John Nurnberger", "Alison Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134393.t003", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tajima_s_D_and_iHS_values_for_CHRNB3_CHRNA6_region_/1510437", "title"=>"Tajima’s D and iHS values for <i>CHRNB3-CHRNA6</i> region.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-13 03:33:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2211742"], "description"=>"<p>Beta, Standard Error (SE), and P-value for all SNPs in the <i>CHRNB3-A6</i> region of the COGA family GWAS and their association with scores on the WAIS Digit Symbol test. Covariates used were age, sex and FTND score. For all tests, 492 individuals were used for the association test.</p><p>Association results with SNPs in <i>CHRNB3-A6</i> region and Scores on the WAIS Digit Symbol test.</p>", "links"=>[], "tags"=>["cocaine dependence", "coga", "Collaborative Studies", "WAIS Digit Symbol", "Loci Associated", "nicotine dependence", "Wechsler Adult Intelligence Scale", "17 SNPs genotyped", "region", "use 1000 Genomes sequence data", "WAIS Information tests", "CHRNA 5 nicotinic receptor gene", "nicotinic receptor gene clusters", "block design", "WAIS digit symbol test results", "evidence selection", "Positive Selection", "reaction time", "test variants", "nicotinic receptor gene cluster", "3 populations", "alcohol dependence", "phenotype", "haplotype score", "chromosomes 8", "Nicotine addiction", "Several loci"], "article_id"=>1510438, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Brooke Sadler", "Gabe Haller", "Howard Edenberg", "Jay Tischfield", "Andy Brooks", "John Kramer", "Marc Schuckit", "John Nurnberger", "Alison Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134393.t004", "stats"=>{"downloads"=>2, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_results_with_SNPs_in_CHRNB3_A6_region_and_Scores_on_the_WAIS_Digit_Symbol_test_/1510438", "title"=>"Association results with SNPs in <i>CHRNB3-A6</i> region and Scores on the WAIS Digit Symbol test.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-13 03:33:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2211739"], "description"=>"<p>A-CTajima’s D andD-F) iHS for the <i>LCT</i> region on chromosome 2, the <i>CHRNA3-B4-A5</i> gene cluster on chromosome 15 and the <i>CHRNB3-A6 gene</i> cluster on chromosome 8 across individuals of European (red), African (Purple) or Asian (green) ancestry. Lines are the 95% confidence intervals as calculated by permutation for iHS and Tajima’s D.</p>", "links"=>[], "tags"=>["cocaine dependence", "coga", "Collaborative Studies", "WAIS Digit Symbol", "Loci Associated", "nicotine dependence", "Wechsler Adult Intelligence Scale", "17 SNPs genotyped", "region", "use 1000 Genomes sequence data", "WAIS Information tests", "CHRNA 5 nicotinic receptor gene", "nicotinic receptor gene clusters", "block design", "WAIS digit symbol test results", "evidence selection", "Positive Selection", "reaction time", "test variants", "nicotinic receptor gene cluster", "3 populations", "alcohol dependence", "phenotype", "haplotype score", "chromosomes 8", "Nicotine addiction", "Several loci"], "article_id"=>1510435, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Brooke Sadler", "Gabe Haller", "Howard Edenberg", "Jay Tischfield", "Andy Brooks", "John Kramer", "Marc Schuckit", "John Nurnberger", "Alison Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134393.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tajima_8217_s_D_and_iHS_Results_/1510435", "title"=>"Tajima’s D and iHS Results.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-08-13 03:33:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2211740"], "description"=>"<p>All SNPs have r<sup>2</sup> value of 0.8 or greater with rs16969968 or rs588765. Significant values and SNP names are bolded.</p><p>Tajima’s D and iHS values for <i>CHRNA5-A3-B4</i> region.</p>", "links"=>[], "tags"=>["cocaine dependence", "coga", "Collaborative Studies", "WAIS Digit Symbol", "Loci Associated", "nicotine dependence", "Wechsler Adult Intelligence Scale", "17 SNPs genotyped", "region", "use 1000 Genomes sequence data", "WAIS Information tests", "CHRNA 5 nicotinic receptor gene", "nicotinic receptor gene clusters", "block design", "WAIS digit symbol test results", "evidence selection", "Positive Selection", "reaction time", "test variants", "nicotinic receptor gene cluster", "3 populations", "alcohol dependence", "phenotype", "haplotype score", "chromosomes 8", "Nicotine addiction", "Several loci"], "article_id"=>1510436, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Brooke Sadler", "Gabe Haller", "Howard Edenberg", "Jay Tischfield", "Andy Brooks", "John Kramer", "Marc Schuckit", "John Nurnberger", "Alison Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134393.t002", "stats"=>{"downloads"=>7, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tajima_s_D_and_iHS_values_for_CHRNA5_A3_B4_region_/1510436", "title"=>"Tajima’s D and iHS values for <i>CHRNA5-A3-B4</i> region.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-13 03:33:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/2211743"], "description"=>"<div><p>Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (<i>CHRN</i>s) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the <i>CHRNA5</i> nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.</p></div>", "links"=>[], "tags"=>["cocaine dependence", "coga", "Collaborative Studies", "WAIS Digit Symbol", "Loci Associated", "nicotine dependence", "Wechsler Adult Intelligence Scale", "17 SNPs genotyped", "region", "use 1000 Genomes sequence data", "WAIS Information tests", "CHRNA 5 nicotinic receptor gene", "nicotinic receptor gene clusters", "block design", "WAIS digit symbol test results", "evidence selection", "Positive Selection", "reaction time", "test variants", "nicotinic receptor gene cluster", "3 populations", "alcohol dependence", "phenotype", "haplotype score", "chromosomes 8", "Nicotine addiction", "Several loci"], "article_id"=>1510439, "categories"=>["Biological Sciences", "Science Policy"], "users"=>["Brooke Sadler", "Gabe Haller", "Howard Edenberg", "Jay Tischfield", "Andy Brooks", "John Kramer", "Marc Schuckit", "John Nurnberger", "Alison Goate"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0134393", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Positive_Selection_on_Loci_Associated_with_Drug_and_Alcohol_Dependence_/1510439", "title"=>"Positive Selection on Loci Associated with Drug and Alcohol Dependence", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-08-13 03:33:02"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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