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Circulation: Cardiovascular Genetics
Year: 2010  |  Volume: 3  |  Issue: 4  |  Page No.: 348 - 357

Genetic Determinants of Major Blood Lipids in Pakistanis Compared With Europeans

D Saleheen, N Soranzo, A Rasheed, H Scharnagl, R Gwilliam, M Alexander, M Inouye, M Zaidi, S Potter, P Haycock, S Bumpstead, S Kaptoge, E Di Angelantonio, N Sarwar, S. E Hunt, N Sheikh, N Shah, M Samuel, S. R Haider, M Murtaza, A Thompson, R Gobin, A Butterworth, U Ahmad, A Hakeem, K. S Zaman, A Kundi, Z Yaqoob, L. A Cheema, N Qamar, A Faruqui, N. H Mallick, M Azhar, A Samad, M Ishaq, S. Z Rasheed, R Jooma, J. H Niazi, A. R Gardezi, N. A Memon, A Ghaffar, F. u Rehman, M. M Hoffmann, W Renner, M. E Kleber, T. B Grammer, J Stephens, A Attwood, K Koch, M Hussain, K Kumar, A Saleem, M. S Daood, A. A Gul, S Abbas, J Zafar, F Shahid, S. M Bhatti, S. S Ali, F Muhammad, G Sagoo, S Bray, R McGinnis, F Dudbridge, B. R Winkelmann, B Boehm, S Thompson, W Ouwehand, W Marz, P Frossard, J Danesh and P. Deloukas    

Abstract: Background—

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

Methods and 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.

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