title: Evaluation of seven common lipid associated loci in a large Indian sib pair study.
abstract: BACKGROUND
  Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance.
  
  
  METHODS
  We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model.
  
  
  RESULTS
  We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10(-7). We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively.
  
  
  CONCLUSIONS
  We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK. s.rafiq@soton.ac.uk
authors.forename: Sajjad
authors.initials: S
authors.lastname: Rafiq
authors.forename: Kranthi Kumar M
authors.initials: KK
authors.lastname: Venkata
authors.forename: Vipin
authors.initials: V
authors.lastname: Gupta
authors.forename: D G
authors.initials: DG
authors.lastname: Vinay
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Spurgeon
authors.forename: Smitha
authors.initials: S
authors.lastname: Parameshwaran
authors.forename: Sandeep N
authors.initials: SN
authors.lastname: Madana
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kinra
authors.forename: Liza
authors.initials: L
authors.lastname: Bowen
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.forename: K Srinath
authors.initials: KS
authors.lastname: Reddy
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D001055:Apolipoproteins B / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008049:Lipase / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D044465:White People / Q000235:genetics
chemical_list: C437704:APOA5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D001055:Apolipoproteins B; C485100:GCKR protein, human; C504173:LIPC protein, human; D008049:Lipase; C548261:LPL protein, human; D008071:Lipoprotein Lipase