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

Saleheen, D; Soranzo, N; Rasheed, A; Scharnagl, H; Gwilliam, R; Alexander, M; Inouye, M; Zaidi, M; Potter, S; Haycock, P; +63 more...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; 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, FORCID logo; Winkelmann, BR; Böehm, B; Thompson, S; Ouwehand, W; März, W; Frossard, P; Danesh, J; Deloukas, P and (2010) Genetic determinants of major blood lipids in Pakistanis compared with Europeans. Circulation Cardiovascular genetics, 3 (4). pp. 348-357. ISSN 1942-325X DOI: 10.1161/CIRCGENETICS.109.906180
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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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