Saleheen, Danish; Soranzo, Nicole; Rasheed, Asif; Scharnagl, Hubert; Gwilliam, Rhian; Alexander, Myriam; Inouye, Michael; Zaidi, Moazzam; Potter, Simon; Haycock, Philip; +63 more... 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; (2010) Genetic determinants of major blood lipids in Pakistanis compared with Europeans. Circulation Cardiovascular genetics, 3 (4). pp. 348-357. ISSN 1942-325X DOI: https://doi.org/10.1161/CIRCGENETICS.109.906180
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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.
Item Type | Article |
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Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
PubMed ID | 20570915 |
ISI | 281006600007 |