Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

Danish Saleheen (Lead / Corresponding author), Nicole Soranzo, Asif Rasheed, Hubert Scharnagl, Rhian Gwilliam, Myriam Alexander, Michael Inouye, Moazzam Zaidi, Simon C. Potter, Philip Haycock, Suzannah Bumpstead, Stephen Kaptoge, Emanuele Di Angelantonio, Nadeem Sarwar, Sarah E. Hunt, Nasir Sheikh, Nabi Shah, Maria Samuel, Shajjia Razi Haider, Muhammed MurtazaAlexander Thompson

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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.
Original languageEnglish
Article number20570915
Pages (from-to)348-357
Number of pages11
JournalCirculation: Cardiovascular Genetics
Early online date22 Jun 2010
DOIs
Publication statusPublished - 1 Aug 2010

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    Saleheen, D., Soranzo, N., Rasheed, A., Scharnagl, H., Gwilliam, R., Alexander, M., Inouye, M., Zaidi, M., Potter, S. C., Haycock, P., Bumpstead, S., Kaptoge, S., Di Angelantonio, E., Sarwar, N., Hunt, S. E., Sheikh, N., Shah, N., Samuel, M., Haider, S. R., ... Thompson, A. (2010). Genetic determinants of major blood lipids in Pakistanis compared with Europeans. Circulation: Cardiovascular Genetics, 348-357. [20570915]. https://doi.org/10.1161/CIRCGENETICS.109.906180