Genetic Determinants of Major Blood Lipids in Pakistanis Compared With Europeans Academic Article uri icon

abstract

  • Evidence is sparse about the genetic determinants of major lipids in Pakistanis.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)).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

  • Saleheen, Danish
  • Soranzo, Nicole
  • Rasheed, Asif
  • Scharnagl, Hubert
  • Gwilliam, Rhian
  • Alexander, Myriam
  • Inouye, Michael
  • Zaidi, Moazzam
  • Potter, Simon
  • Haycock, Philip
  • Bumpstead, Suzanna
  • Kaptoge, Stephen
  • Di Angelantonio, Emanuele
  • Sarwar, Nadeem
  • Hunt, Sarah E
  • Sheikh, Nasir
  • Shah, Nabi
  • Samuel, Maria
  • Haider, Shajjia Razi
  • Murtaza, Muhammed
  • Thompson, Alexander
  • Gobin, Reeta
  • Butterworth, Adam
  • Ahmad, Usman
  • Hakeem, Abdul
  • Zaman, Khan Shah
  • Kundi, Assadullah
  • Yaqoob, Zia
  • Cheema, Liaquat Ali
  • Qamar, Nadeem
  • Faruqui, Azhar
  • Mallick, Nadeem Hayat
  • Azhar, Muhammad
  • Samad, Abdus
  • Ishaq, Muhammad
  • Rasheed, Syed Zahed
  • Jooma, Rashid
  • Niazi, Jawaid Hassan
  • Gardezi, Ali Raza
  • Memon, Nazir Ahmed
  • Ghaffar, Abdul
  • Rehman, Fazal-ur
  • Hoffmann, Michael Marcus
  • Renner, Wilfried
  • Kleber, Marcus E
  • Grammer, Tanja B
  • Stephens, Jonathon
  • Attwood, Anthony
  • Koch, Kerstin
  • Hussain, Mustafa
  • Kumar, Kishore
  • Saleem, Asim
  • Kumar, Kishwar
  • Daood, Muhammad Salman
  • Gul, Aftab Alam
  • Abbas, Shahid
  • Zafar, Junaid
  • Shahid, Faisal
  • Bhatti, Shahzad Majeed
  • Ali, Syed Saadat
  • Muhammad, Fahim
  • Sagoo, Gurdeep
  • Bray, Sarah
  • McGinnis, Ralph
  • Dudbridge, Frank
  • Winkelmann, Bernhard R
  • Böehm, Bernhard
  • Thompson, Simon
  • Ouwehand, Willem
  • März, Winfried
  • Frossard, Philippe
  • Danesh, John
  • Deloukas, Panos

publication date

  • August 2010