Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans
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{"title"=>"Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans", "type"=>"journal", "authors"=>[{"first_name"=>"Amy R.", "last_name"=>"Bentley", "scopus_author_id"=>"54962480000"}, {"first_name"=>"Guanjie", "last_name"=>"Chen", "scopus_author_id"=>"8050014800"}, {"first_name"=>"Daniel", "last_name"=>"Shriner", "scopus_author_id"=>"7004202273"}, {"first_name"=>"Ayo P.", "last_name"=>"Doumatey", "scopus_author_id"=>"6507897813"}, {"first_name"=>"Jie", "last_name"=>"Zhou", "scopus_author_id"=>"56889899600"}, {"first_name"=>"Hanxia", "last_name"=>"Huang", "scopus_author_id"=>"14323522200"}, {"first_name"=>"James C.", "last_name"=>"Mullikin", "scopus_author_id"=>"6603704418"}, {"first_name"=>"Robert W.", "last_name"=>"Blakesley", "scopus_author_id"=>"6603826631"}, {"first_name"=>"Nancy F.", "last_name"=>"Hansen", "scopus_author_id"=>"7201389828"}, {"first_name"=>"Gerard G.", "last_name"=>"Bouffard", "scopus_author_id"=>"6602758494"}, {"first_name"=>"Praveen F.", "last_name"=>"Cherukuri", "scopus_author_id"=>"6507941191"}, {"first_name"=>"Baishali", "last_name"=>"Maskeri", "scopus_author_id"=>"6506358246"}, {"first_name"=>"Alice C.", "last_name"=>"Young", "scopus_author_id"=>"7403881618"}, {"first_name"=>"Adebowale", "last_name"=>"Adeyemo", "scopus_author_id"=>"56800223700"}, {"first_name"=>"Charles N.", "last_name"=>"Rotimi", "scopus_author_id"=>"7006238725"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"372738237", "sgr"=>"84897412408", "issn"=>"15537404", "pmid"=>"24603370", "scopus"=>"2-s2.0-84897412408", "doi"=>"10.1371/journal.pgen.1004190", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)"}, "id"=>"b464e5f8-a03a-3c8e-9f99-d04201c2d405", "abstract"=>"<title>Author Summary</title><p>Most of the work on the genetic epidemiology of serum lipids in African Americans (AA) has focused on replicating findings that were identified in European ancestry individuals. While this can be very informative about the generalizability of lipids loci across populations, African ancestry-specific variation will be missed using this approach. Our aim was to comprehensively evaluate five lipid candidate genes in an AA population, from the identification of variants of interest to population-level analysis of high-density lipoprotein cholesterol (HDLC) and triglycerides (TG). We sequenced five genes in individuals with extreme lipids (n = 48) drawn from a population-based study of AA. The variants identified were genotyped in 1,694 AA and analyzed. Notable among the findings were the observation of ancestry specific effect for several variants in the <italic>LPL</italic> gene among these admixed individuals, with a greater effect observed among those with European ancestry in this region. These associations were further elucidated by replication in West Africans. By beginning with the sequence variation present among AA, investigating ancestry effects, and seeking replication in West Africans, we were able to comprehensively evaluate these candidate genes with a focus on African ancestry individuals.</p>", "link"=>"http://www.mendeley.com/research/genebased-sequencing-identifies-lipidinfluencing-variants-ethnicityspecific-effects-african-american", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>9, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>4, "Student > Master"=>2, "Student > Bachelor"=>1, "Lecturer"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>13, "Social Sciences"=>1, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "Nigeria"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1410949"], "description"=>"<p><i>Abbreviations: Body Mass Index (BMI); <sup>1</sup>Mean (± standard deviation) given except where indicated; <sup>2</sup>median and interquartile range given due to non-normality.</i></p>", "links"=>[], "tags"=>["Biochemistry", "lipids", "genetics", "Human genetics", "epidemiology", "Genetic epidemiology"], "article_id"=>954579, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Amy R. Bentley", "Guanjie Chen", "Daniel Shriner", "Ayo P. Doumatey", "Jie Zhou", "Hanxia Huang", "James C. Mullikin", "Robert W. Blakesley", "Nancy F. Hansen", "Gerard G. Bouffard", "Praveen F. Cherukuri", "Baishali Maskeri", "Alice C. Young", "Adebowale Adeyemo", "Charles N. Rotimi"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004190.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Participant_characteristics_1_/954579", "title"=>"Participant characteristics<sup>1</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-06 04:29:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1410950", "https://ndownloader.figshare.com/files/1410951", "https://ndownloader.figshare.com/files/1410952", "https://ndownloader.figshare.com/files/1410953", "https://ndownloader.figshare.com/files/1410954"], "description"=>"<div><p>Although a considerable proportion of serum lipids loci identified in European ancestry individuals (EA) replicate in African Americans (AA), interethnic differences in the distribution of serum lipids suggest that some genetic determinants differ by ethnicity. We conducted a comprehensive evaluation of five lipid candidate genes to identify variants with ethnicity-specific effects. We sequenced <i>ABCA1</i>, <i>LCAT</i>, <i>LPL</i>, <i>PON1</i>, and <i>SERPINE1</i> in 48 AA individuals with extreme serum lipid concentrations (high HDLC/low TG or low HDLC/high TG). Identified variants were genotyped in the full population-based sample of AA (n = 1694) and tested for an association with serum lipids. rs328 (<i>LPL</i>) and correlated variants were associated with higher HDLC and lower TG. Interestingly, a stronger effect was observed on a “European” vs. “African” genetic background at this locus. To investigate this effect, we evaluated the region among West Africans (WA). For TG, the effect size among WA was the same in AA with only African local ancestry (2–3% lower TG), while the larger association among AA with local European ancestry matched previous reports in EA (10%). For HDLC, there was no association with rs328 in AA with only African local ancestry or in WA, while the association among AA with European local ancestry was much greater than what has been observed for EA (15 vs. ∼5 mg/dl), suggesting an interaction with an environmental or genetic factor that differs by ethnicity. Beyond this ancestry effect, the importance of African ancestry-focused, sequence-based work was also highlighted by serum lipid associations of variants that were in higher frequency (or present only) among those of African ancestry. By beginning our study with the sequence variation present in AA individuals, investigating local ancestry effects, and seeking replication in WA, we were able to comprehensively evaluate the role of a set of candidate genes in serum lipids in AA.</p></div>", "links"=>[], "tags"=>["Biochemistry", "lipids", "genetics", "Human genetics", "epidemiology", "Genetic epidemiology", "sequencing", "identifies", "lipid-influencing", "variants", "ethnicity-specific", "african"], "article_id"=>954580, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Amy R. Bentley", "Guanjie Chen", "Daniel Shriner", "Ayo P. Doumatey", "Jie Zhou", "Hanxia Huang", "James C. Mullikin", "Robert W. Blakesley", "Nancy F. Hansen", "Gerard G. Bouffard", "Praveen F. Cherukuri", "Baishali Maskeri", "Alice C. Young", "Adebowale Adeyemo", "Charles N. Rotimi"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1004190.s001", "https://dx.doi.org/10.1371/journal.pgen.1004190.s002", "https://dx.doi.org/10.1371/journal.pgen.1004190.s003", "https://dx.doi.org/10.1371/journal.pgen.1004190.s004", "https://dx.doi.org/10.1371/journal.pgen.1004190.s005"], "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_Based_Sequencing_Identifies_Lipid_Influencing_Variants_with_Ethnicity_Specific_Effects_in_African_Americans_/954580", "title"=>"Gene-Based Sequencing Identifies Lipid-Influencing Variants with Ethnicity-Specific Effects in African Americans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-03-06 04:29:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1410947"], "description"=>"<p>Difference in serum HDLC and logTG with the variant genotype for African Americans with 0, 1, or 2 African ancestry alleles at this locus, and West African individuals. Results for other <i>LPL</i> variants in LD with rs328 were similar.</p>", "links"=>[], "tags"=>["Biochemistry", "lipids", "genetics", "Human genetics", "epidemiology", "Genetic epidemiology", "rs328", "genotype", "ancestry", "african", "americans"], "article_id"=>954577, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Amy R. Bentley", "Guanjie Chen", "Daniel Shriner", "Ayo P. Doumatey", "Jie Zhou", "Hanxia Huang", "James C. Mullikin", "Robert W. Blakesley", "Nancy F. Hansen", "Gerard G. Bouffard", "Praveen F. Cherukuri", "Baishali Maskeri", "Alice C. Young", "Adebowale Adeyemo", "Charles N. Rotimi"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004190.g001", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Serum_lipids_by_rs328_genotype_and_local_ancestry_in_African_Americans_and_West_Africans_/954577", "title"=>"Serum lipids by rs328 genotype and local ancestry in African Americans and West Africans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-03-06 04:29:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1410948"], "description"=>"<p>Abbreviations: Additive (Add), Chromosome (Chr), Dominant (Dom), Minor Allele Frequency (MAF), High-density Lipoprotein Cholesterol (HDLC), Recessive (Rec), Log-transformed Triglycerides (logTG); <sup>1</sup>Build 37 position; <sup>2</sup> βs are given for the minor (“Alt”) allele. TG values were log-transformed: β values represent the percent change in TG. <sup>3</sup>Correction for multiple hypotheses conducted by calculating the effective degrees of freedom using the covariance matrix for variants in each gene. All P-values have been multiplied by the effective degrees of freedom for that gene (see methods and reference<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004190#pgen.1004190-Ramos1\" target=\"_blank\">[54]</a>); <sup>4</sup>Similar results observed for the following CVs in high LD (R<sup>2</sup>>0.8) with listed SNP: rs114851717 (rs138618449, rs148714575, rs115761095, rs76729624), rs256 (rs271), rs328 (rs325, rs117199990, rs145391587, rs75278536, rs77069344, rs11570891, rs1803924, rs3735964), rs1059611 (rs149865365), rs2515602 (rs2472386), rs1800977 (rs2437817, rs2243312).CVs in LD (R<sup>2</sup>>0.6); <sup>5</sup>These associations would no longer be statistically significant if adjusted for model selection (4 genetic models compared).</p>", "links"=>[], "tags"=>["Biochemistry", "lipids", "genetics", "Human genetics", "epidemiology", "Genetic epidemiology", "variants", "genes", "serum", "african", "americans"], "article_id"=>954578, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Amy R. Bentley", "Guanjie Chen", "Daniel Shriner", "Ayo P. Doumatey", "Jie Zhou", "Hanxia Huang", "James C. Mullikin", "Robert W. Blakesley", "Nancy F. Hansen", "Gerard G. Bouffard", "Praveen F. Cherukuri", "Baishali Maskeri", "Alice C. Young", "Adebowale Adeyemo", "Charles N. Rotimi"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004190.t002", "stats"=>{"downloads"=>1, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Common_variants_in_candidate_genes_associated_with_serum_lipids_in_African_Americans_n_8202_8202_1694_/954578", "title"=>"Common variants in candidate genes associated with serum lipids in African Americans (n = 1694).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-03-06 04:29:42"}

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Relative Metric

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