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, D
  • Soranzo, N
  • Rasheed, A
  • Scharnagl, H
  • Gwilliam, R
  • Alexander, M
  • Inouye, M
  • Zaidi, M
  • Potter, S
  • Haycock, P
  • Bumpstead, S
  • Kaptoge, S
  • Di Angelantonio, E
  • Sarwar, N
  • Hunt, SE
  • Sheikh, N
  • Shah, N
  • Samuel, M
  • Haider, SR
  • Murtaza, M
  • Thompson, A
  • Gobin, R
  • Butterworth, A
  • Ahmad, U
  • Hakeem, A
  • Zaman, KS
  • Kundi, A
  • Yaqoob, Z
  • Cheema, LA
  • Qamar, N
  • Faruqui, A
  • Mallick, NH
  • Azhar, M
  • Samad, A
  • Ishaq, M
  • Rasheed, SZ
  • Jooma, R
  • Niazi, JH
  • Gardezi, AR
  • Memon, NA
  • Ghaffar, A
  • Rehman, F.-u
  • Hoffmann, MM
  • Renner, W
  • Kleber, ME
  • Grammer, TB
  • Stephens, J
  • Attwood, A
  • Koch, K
  • Hussain, M
  • Kumar, K
  • Saleem, A
  • Kumar, K
  • Daood, MS
  • Gul, AA
  • Abbas, S
  • Zafar, J
  • Shahid, F
  • Bhatti, SM
  • Ali, SS
  • Muhammad, F
  • Sagoo, G
  • Bray, S
  • McGinnis, R
  • Dudbridge, F
  • Winkelmann, BR
  • Boehm, B
  • Thompson, S
  • Ouwehand, W
  • Marz, W
  • Frossard, P
  • Danesh, J
  • Deloukas, P

publication date

  • August 1, 2010