title: Fine-mapping in African Americans of 8 recently discovered genetic loci for plasma lipids: the Jackson Heart Study.
abstract: BACKGROUND
  Genome-wide association studies in cohorts of European descent have identified novel genomic regions as associated with lipids, but their relevance in African Americans remains unclear.
  
  
  RESULTS
  We genotyped 8 index single nucleotide polymorphisms (SNPs) and 488 tagging SNPs across 8 novel lipid loci in the Jackson Heart Study, a community-based cohort of 4605 African Americans. For each trait, we calculated residuals adjusted for age, sex, and global ancestry and performed multivariable linear regression to detect genotype-phenotype association with adjustment for local ancestry. To explore admixture effects, we conducted stratified analyses in individuals with a high probability of 2 African ancestral alleles or at least 1 European allele at each locus. We confirmed 2 index SNPs as associated with lipid traits in African Americans, with suggestive association for 3 more. However, the effect sizes for 4 of the 5 associated SNPs were larger in the European local ancestry subgroup compared with the African local ancestry subgroup, suggesting that the replication is driven by European ancestry segments. Through fine-mapping, we discovered 3 new SNPs with significant associations, 2 with consistent effect on triglyceride levels across ancestral groups: rs636523 near DOCK7/ANGPTL3 and rs780093 in GCKR. African linkage disequilibrium patterns did not assist in narrowing association signals.
  
  
  CONCLUSIONS
  We confirm that 5 genetic regions associated with lipid traits in European-derived populations are relevant in African Americans. To further evaluate these loci, fine-mapping in larger African American cohorts and/or resequencing will be required.
authors.affiliation: Massachusetts General Hospital, Boston, MA 02115, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Keebler
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Deo
authors.forename: Aarti
authors.initials: A
authors.lastname: Surti
authors.forename: David
authors.initials: D
authors.lastname: Konieczkowski
authors.forename: Candace
authors.initials: C
authors.lastname: Guiducci
authors.forename: Noel
authors.initials: N
authors.lastname: Burtt
authors.forename: Sarah G
authors.initials: SG
authors.lastname: Buxbaum
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sarpong
authors.forename: Michael W
authors.initials: MW
authors.lastname: Steffes
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002874:Chromosome Mapping / Q000379:methods*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000208:ethnology / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D008055:Lipids