toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Record Links
Author (up) Wu, Y.; Waite, L.L.; Jackson, A.U.; Sheu, W.H.-H.; Buyske, S.; Absher, D.; Arnett, D.K.; Boerwinkle, E.; Bonnycastle, L.L.; Carty, C.L.; Cheng, I.; Cochran, B.; Croteau-Chonka, D.C.; Dumitrescu, L.; Eaton, C.B.; Franceschini, N.; Guo, X.; Henderson, B.E.; Hindorff, L.A.; Kim, E.; Kinnunen, L.; Komulainen, P.; Lee, W.-J.; Le Marchand, L.; Lin, Y.; Lindstrom, J.; Lingaas-Holmen, O.; Mitchell, S.L.; Narisu, N.; Robinson, J.G.; Schumacher, F.; Stancakova, A.; Sundvall, J.; Sung, Y.-J.; Swift, A.J.; Wang, W.-C.; Wilkens, L.; Wilsgaard, T.; Young, A.M.; Adair, L.S.; Ballantyne, C.M.; Buzkova, P.; Chakravarti, A.; Collins, F.S.; Duggan, D.; Feranil, A.B.; Ho, L.-T.; Hung, Y.-J.; Hunt, S.C.; Hveem, K.; Juang, J.-M.J.; Kesaniemi, A.Y.; Kuusisto, J.; Laakso, M.; Lakka, T.A.; Lee, I.-T.; Leppert, M.F.; Matise, T.C.; Moilanen, L.; Njolstad, I.; Peters, U.; Quertermous, T.; Rauramaa, R.; Rotter, J.I.; Saramies, J.; Tuomilehto, J.; Uusitupa, M.; Wang, T.-D.; Boehnke, M.; Haiman, C.A.; Chen, Y.-D.I.; Kooperberg, C.; Assimes, T.L.; Crawford, D.C.; Hsiung, C.A.; North, K.E.; Mohlke, K.L. url  doi
  Title Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained Type Journal Article
  Year 2013 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 9 Issue 3 Pages e1003379  
  Keywords African Americans/genetics; Apolipoproteins A/*genetics; Cholesterol, HDL/blood/genetics; Cholesterol, LDL/blood/genetics; European Continental Ancestry Group/genetics; *Genome-Wide Association Study; Humans; Lipoproteins, HDL/blood/genetics; Lipoproteins, LDL/blood/genetics; Proprotein Convertases/*genetics; Serine Endopeptidases/*genetics; Triglycerides/blood/genetics  
  Abstract Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 x 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.  
  Address Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23555291; PMC3605054 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1385  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: