title: Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.
abstract: BACKGROUND
  The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations.
  
  
  RESULTS
  We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein gene (p=2.43×10(-08)). Furthermore, three European loci for TGs (APOA5, GCKR and LPL), and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We used cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalised to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans.
  
  
  CONCLUSIONS
  This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; used the interpopulation heterogeneity to significantly restrict three previously known European GWA signals, and surveyed whether the European lipid GWA SNPs extend to the Mexican population.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at UCLA, Gonda Center, Room 6335B, 695 Charles E. Young Drive South, Los Angeles, CA 90095-7088, USA.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.forename: Elina
authors.initials: E
authors.lastname: Nikkola
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Deere
authors.forename: Ivette
authors.initials: I
authors.lastname: Cruz-Bautista
authors.forename: Olimpia
authors.initials: O
authors.lastname: Arellano-Campos
authors.forename: Linda Liliana
authors.initials: LL
authors.lastname: Muñoz-Hernandez
authors.forename: Lizeth
authors.initials: L
authors.lastname: Gomez-Munguia
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Ordoñez-Sánchez
authors.forename: Prasad M V Linga
authors.initials: PM
authors.lastname: Reddy
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Niina
authors.initials: N
authors.lastname: Matikainen
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Laura
authors.initials: L
authors.lastname: Riba
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: Teresa
authors.initials: T
authors.lastname: Tusie-Luna
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
mesh_terms: D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000097:blood / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000208:ethnology / Q000235:genetics*; D052456:Hypoalphalipoproteinemias / Q000208:ethnology / Q000235:genetics*; D007198:Indians, North American / Q000235:genetics*; D015810:Linkage Disequilibrium; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008800:Mexico; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014280:Triglycerides / Q000097:blood / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D014280:Triglycerides