title: Genetic determinants of major blood lipids in Pakistanis compared with Europeans.
abstract: BACKGROUND
  Evidence is sparse about the genetic determinants of major lipids in Pakistanis.
  
  
  RESULTS
  Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)).
  
  
  CONCLUSIONS
  Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.
authors.affiliation: Center for Non-Communicable Diseases Karachi, Pakistan. danish.saleheen@cncdpk.com
authors.forename: Danish
authors.initials: D
authors.lastname: Saleheen
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Asif
authors.initials: A
authors.lastname: Rasheed
authors.forename: Hubert
authors.initials: H
authors.lastname: Scharnagl
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Myriam
authors.initials: M
authors.lastname: Alexander
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Moazzam
authors.initials: M
authors.lastname: Zaidi
authors.forename: Simon
authors.initials: S
authors.lastname: Potter
authors.forename: Philip
authors.initials: P
authors.lastname: Haycock
authors.forename: Suzanna
authors.initials: S
authors.lastname: Bumpstead
authors.forename: Stephen
authors.initials: S
authors.lastname: Kaptoge
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Nadeem
authors.initials: N
authors.lastname: Sarwar
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hunt
authors.forename: Nasir
authors.initials: N
authors.lastname: Sheikh
authors.forename: Nabi
authors.initials: N
authors.lastname: Shah
authors.forename: Maria
authors.initials: M
authors.lastname: Samuel
authors.forename: Shajjia Razi
authors.initials: SR
authors.lastname: Haider
authors.forename: Muhammed
authors.initials: M
authors.lastname: Murtaza
authors.forename: Alexander
authors.initials: A
authors.lastname: Thompson
authors.forename: Reeta
authors.initials: R
authors.lastname: Gobin
authors.forename: Adam
authors.initials: A
authors.lastname: Butterworth
authors.forename: Usman
authors.initials: U
authors.lastname: Ahmad
authors.forename: Abdul
authors.initials: A
authors.lastname: Hakeem
authors.forename: Khan Shah
authors.initials: KS
authors.lastname: Zaman
authors.forename: Assadullah
authors.initials: A
authors.lastname: Kundi
authors.forename: Zia
authors.initials: Z
authors.lastname: Yaqoob
authors.forename: Liaquat Ali
authors.initials: LA
authors.lastname: Cheema
authors.forename: Nadeem
authors.initials: N
authors.lastname: Qamar
authors.forename: Azhar
authors.initials: A
authors.lastname: Faruqui
authors.forename: Nadeem Hayat
authors.initials: NH
authors.lastname: Mallick
authors.forename: Muhammad
authors.initials: M
authors.lastname: Azhar
authors.forename: Abdus
authors.initials: A
authors.lastname: Samad
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ishaq
authors.forename: Syed Zahed
authors.initials: SZ
authors.lastname: Rasheed
authors.forename: Rashid
authors.initials: R
authors.lastname: Jooma
authors.forename: Jawaid Hassan
authors.initials: JH
authors.lastname: Niazi
authors.forename: Ali Raza
authors.initials: AR
authors.lastname: Gardezi
authors.forename: Nazir Ahmed
authors.initials: NA
authors.lastname: Memon
authors.forename: Abdul
authors.initials: A
authors.lastname: Ghaffar
authors.forename: Fazal-ur
authors.initials: FU
authors.lastname: Rehman
authors.forename: Michael Marcus
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Jonathon
authors.initials: J
authors.lastname: Stephens
authors.forename: Anthony
authors.initials: A
authors.lastname: Attwood
authors.forename: Kerstin
authors.initials: K
authors.lastname: Koch
authors.forename: Mustafa
authors.initials: M
authors.lastname: Hussain
authors.forename: Kishore
authors.initials: K
authors.lastname: Kumar
authors.forename: Asim
authors.initials: A
authors.lastname: Saleem
authors.forename: Kishwar
authors.initials: K
authors.lastname: Kumar
authors.forename: Muhammad Salman
authors.initials: MS
authors.lastname: Daood
authors.forename: Aftab Alam
authors.initials: AA
authors.lastname: Gul
authors.forename: Shahid
authors.initials: S
authors.lastname: Abbas
authors.forename: Junaid
authors.initials: J
authors.lastname: Zafar
authors.forename: Faisal
authors.initials: F
authors.lastname: Shahid
authors.forename: Shahzad Majeed
authors.initials: SM
authors.lastname: Bhatti
authors.forename: Syed Saadat
authors.initials: SS
authors.lastname: Ali
authors.forename: Fahim
authors.initials: F
authors.lastname: Muhammad
authors.forename: Gurdeep
authors.initials: G
authors.lastname: Sagoo
authors.forename: Sarah
authors.initials: S
authors.lastname: Bray
authors.forename: Ralph
authors.initials: R
authors.lastname: McGinnis
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Bernhard R
authors.initials: BR
authors.lastname: Winkelmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Böehm
authors.forename: Simon
authors.initials: S
authors.lastname: Thompson
authors.forename: Willem
authors.initials: W
authors.lastname: Ouwehand
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Philippe
authors.initials: P
authors.lastname: Frossard
authors.forename: John
authors.initials: J
authors.lastname: Danesh
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000208:ethnology / Q000235:genetics; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide
chemical_list: D008055:Lipids