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

Danish Saleheen; 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 Murtaza; Alexander  Thompson

doi:10.1161/CIRCGENETICS.109.906180

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 Murtaza

Alexander Thompson

Population Health and Genomics

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

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 language	English
Article number	20570915
Pages (from-to)	348-357
Number of pages	11
Journal	Circulation: Cardiovascular Genetics
Early online date	22 Jun 2010
DOIs	https://doi.org/10.1161/CIRCGENETICS.109.906180
Publication status	Published - 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. Article 20570915. https://doi.org/10.1161/CIRCGENETICS.109.906180

@article{c29ed4ab9c144a0e95428455650ef3fa,

title = "Genetic determinants of major blood lipids in Pakistanis compared with Europeans.",

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.",

author = "Danish Saleheen and Nicole Soranzo and Asif Rasheed and Hubert Scharnagl and Rhian Gwilliam and Myriam Alexander and Michael Inouye and Moazzam Zaidi and Potter, \{Simon C.\} and Philip Haycock and Suzannah Bumpstead and Stephen Kaptoge and \{Di Angelantonio\}, Emanuele and Nadeem Sarwar and Hunt, \{Sarah E.\} and Nasir Sheikh and Nabi Shah and Maria Samuel and Haider, \{Shajjia Razi\} and Muhammed Murtaza and Alexander Thompson",

year = "2010",

month = aug,

day = "1",

doi = "10.1161/CIRCGENETICS.109.906180",

language = "English",

pages = "348--357",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

publisher = "Lippincott Williams and Wilkins Ltd.",

}

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

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 -

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

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