TY - JOUR
T1 - Genetic determinants of major blood lipids in Pakistanis compared with Europeans.
AU - Saleheen, Danish
AU - Soranzo, Nicole
AU - Rasheed, Asif
AU - Scharnagl, Hubert
AU - Gwilliam, Rhian
AU - Alexander, Myriam
AU - Inouye, Michael
AU - Zaidi, Moazzam
AU - Potter, Simon C.
AU - Haycock, Philip
AU - Bumpstead, Suzannah
AU - Kaptoge, Stephen
AU - Di Angelantonio, Emanuele
AU - Sarwar, Nadeem
AU - Hunt, Sarah E.
AU - Sheikh, Nasir
AU - Shah, Nabi
AU - Samuel, Maria
AU - Haider, Shajjia Razi
AU - Murtaza, Muhammed
AU - Thompson, Alexander
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
U2 - 10.1161/CIRCGENETICS.109.906180
DO - 10.1161/CIRCGENETICS.109.906180
M3 - Article
SN - 1942-325X
SP - 348
EP - 357
JO - Circulation: Cardiovascular Genetics
JF - Circulation: Cardiovascular Genetics
M1 - 20570915
ER -