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 Potter; Philip Haycock; Suzanna Bumpstead; Stephen Kaptoge; Emanuele Di Angelantonio; Nadeem Sarwar; Sarah E. Hunt; Nasir Sheikh; Nabi Shah; Maria Samuel; Shajjia Razi Haider; Muhammed Murtaza; Alexander Thompson; Reeta Gobin; Adam Butterworth; Usman Ahmad; Abdul Hakeem; Khan Shah Zaman; Assadullah Kundi; Zia Yaqoob; Liaquat Ali Cheema; Nadeem Qamar; Azhar Faruqui; Nadeem Hayat Mallick; Muhammad Azhar; Abdus Samad; Muhammad Ishaq; Syed Zahed Rasheed; Rashid Jooma; Jawaid Hassan Niazi; Ali Raza Gardezi; Nazir Ahmed Memon; Abdul Ghaffar; Fazal Ur Rehman; Michael Marcus Hoffmann; Wilfried Renner; Marcus E. Kleber; Tanja B. Grammer; Jonathon Stephens; Anthony Attwood; Kerstin Koch; Mustafa Hussain; Kishore Kumar; Asim Saleem; Kishwar Kumar; Muhammad Salman Daood; Aftab Alam Gul; Shahid Abbas; Junaid Zafar; Faisal Shahid; Shahzad Majeed Bhatti; Syed Saadat Ali; Muhammad Fahim; Gurdeep Sagoo; Sarah Bray; Ralph McGinnis; Frank Dudbridge; Bernhard R. Winkelmann; Bernhard Böehm; Simon Thompson; Willem Ouwehand; Winfried März; Philippe Frossard; John Danesh; Panos Deloukas

doi:10.1161/CIRCGENETICS.109.906180

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 Potter, Philip Haycock, Suzanna Bumpstead, Stephen Kaptoge, Emanuele Di Angelantonio, Nadeem Sarwar, Sarah E. Hunt, Nasir Sheikh, Nabi Shah, Maria Samuel, Shajjia Razi Haider, Muhammed MurtazaAlexander Thompson, Reeta Gobin, Adam Butterworth, Usman Ahmad, Abdul Hakeem, Khan Shah Zaman, Assadullah Kundi, Zia Yaqoob, Liaquat Ali Cheema, Nadeem Qamar, Azhar Faruqui, Nadeem Hayat Mallick, Muhammad Azhar, Abdus Samad, Muhammad Ishaq, Syed Zahed Rasheed, Rashid Jooma, Jawaid Hassan Niazi, Ali Raza Gardezi, Nazir Ahmed Memon, Abdul Ghaffar, Fazal Ur Rehman, Michael Marcus Hoffmann, Wilfried Renner, Marcus E. Kleber, Tanja B. Grammer, Jonathon Stephens, Anthony Attwood, Kerstin Koch, Mustafa Hussain, Kishore Kumar, Asim Saleem, Kishwar Kumar, Muhammad Salman Daood, Aftab Alam Gul, Shahid Abbas, Junaid Zafar, Faisal Shahid, Shahzad Majeed Bhatti, Syed Saadat Ali, Muhammad Fahim, Gurdeep Sagoo, Sarah Bray, Ralph McGinnis, Frank Dudbridge, Bernhard R. Winkelmann, Bernhard Böehm, Simon Thompson, Willem Ouwehand, Winfried März, Philippe Frossard, John Danesh, Panos Deloukas

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

23 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
Pages (from-to)	348-357
Number of pages	10
Journal	Circulation: Cardiovascular Genetics
Volume	3
Issue number	4
DOIs	https://doi.org/10.1161/CIRCGENETICS.109.906180
Publication status	Published - Aug 2010
Externally published	Yes

Keywords

GWAS
Gene
HDL-C
IBC-array
LDL-C
Lipids
Meta-analysis
Pakistan
Population structure
Triglyceride

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10.1161/CIRCGENETICS.109.906180

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Saleheen, D., Soranzo, N., Rasheed, A., Scharnagl, H., Gwilliam, R., Alexander, M., Inouye, M., Zaidi, M., Potter, S., Haycock, P., Bumpstead, S., Kaptoge, S., Di Angelantonio, E., Sarwar, N., Hunt, S. E., Sheikh, N., Shah, N., Samuel, M., Haider, S. R., ... Deloukas, P. (2010). Genetic determinants of major blood lipids in pakistanis compared with Europeans. Circulation: Cardiovascular Genetics, 3(4), 348-357. https://doi.org/10.1161/CIRCGENETICS.109.906180

@article{b01abce22fba4081b196c186340fa13d,

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.",

keywords = "GWAS, Gene, HDL-C, IBC-array, LDL-C, Lipids, Meta-analysis, Pakistan, Population structure, Triglyceride",

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 Simon Potter and Philip Haycock and Suzanna 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 and Reeta Gobin and Adam Butterworth and Usman Ahmad and Abdul Hakeem and Zaman, {Khan Shah} and Assadullah Kundi and Zia Yaqoob and Cheema, {Liaquat Ali} and Nadeem Qamar and Azhar Faruqui and Mallick, {Nadeem Hayat} and Muhammad Azhar and Abdus Samad and Muhammad Ishaq and Rasheed, {Syed Zahed} and Rashid Jooma and Niazi, {Jawaid Hassan} and Gardezi, {Ali Raza} and Memon, {Nazir Ahmed} and Abdul Ghaffar and Rehman, {Fazal Ur} and Hoffmann, {Michael Marcus} and Wilfried Renner and Kleber, {Marcus E.} and Grammer, {Tanja B.} and Jonathon Stephens and Anthony Attwood and Kerstin Koch and Mustafa Hussain and Kishore Kumar and Asim Saleem and Kishwar Kumar and Daood, {Muhammad Salman} and Gul, {Aftab Alam} and Shahid Abbas and Junaid Zafar and Faisal Shahid and Bhatti, {Shahzad Majeed} and Ali, {Syed Saadat} and Muhammad Fahim and Gurdeep Sagoo and Sarah Bray and Ralph McGinnis and Frank Dudbridge and Winkelmann, {Bernhard R.} and Bernhard B{\"o}ehm and Simon Thompson and Willem Ouwehand and Winfried M{\"a}rz and Philippe Frossard and John Danesh and Panos Deloukas",

year = "2010",

month = aug,

doi = "10.1161/CIRCGENETICS.109.906180",

language = "English",

volume = "3",

pages = "348--357",

journal = "Circulation: Cardiovascular Genetics",

issn = "1942-325X",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "4",

}

Saleheen, D, Soranzo, N, Rasheed, A, Scharnagl, H, Gwilliam, R, Alexander, M, Inouye, M, Zaidi, M, Potter, S, 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, 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, FU, 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, Fahim, M, Sagoo, G, Bray, S, McGinnis, R, Dudbridge, F, Winkelmann, BR, Böehm, B, Thompson, S, Ouwehand, W, März, W, Frossard, P, Danesh, J & Deloukas, P 2010, 'Genetic determinants of major blood lipids in pakistanis compared with Europeans', Circulation: Cardiovascular Genetics, vol. 3, no. 4, 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

AU - Haycock, Philip

AU - Bumpstead, Suzanna

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

AU - Gobin, Reeta

AU - Butterworth, Adam

AU - Ahmad, Usman

AU - Hakeem, Abdul

AU - Zaman, Khan Shah

AU - Kundi, Assadullah

AU - Yaqoob, Zia

AU - Cheema, Liaquat Ali

AU - Qamar, Nadeem

AU - Faruqui, Azhar

AU - Mallick, Nadeem Hayat

AU - Azhar, Muhammad

AU - Samad, Abdus

AU - Ishaq, Muhammad

AU - Rasheed, Syed Zahed

AU - Jooma, Rashid

AU - Niazi, Jawaid Hassan

AU - Gardezi, Ali Raza

AU - Memon, Nazir Ahmed

AU - Ghaffar, Abdul

AU - Rehman, Fazal Ur

AU - Hoffmann, Michael Marcus

AU - Renner, Wilfried

AU - Kleber, Marcus E.

AU - Grammer, Tanja B.

AU - Stephens, Jonathon

AU - Attwood, Anthony

AU - Koch, Kerstin

AU - Hussain, Mustafa

AU - Kumar, Kishore

AU - Saleem, Asim

AU - Kumar, Kishwar

AU - Daood, Muhammad Salman

AU - Gul, Aftab Alam

AU - Abbas, Shahid

AU - Zafar, Junaid

AU - Shahid, Faisal

AU - Bhatti, Shahzad Majeed

AU - Ali, Syed Saadat

AU - Fahim, Muhammad

AU - Sagoo, Gurdeep

AU - Bray, Sarah

AU - McGinnis, Ralph

AU - Dudbridge, Frank

AU - Winkelmann, Bernhard R.

AU - Böehm, Bernhard

AU - Thompson, Simon

AU - Ouwehand, Willem

AU - März, Winfried

AU - Frossard, Philippe

AU - Danesh, John

AU - Deloukas, Panos

PY - 2010/8

Y1 - 2010/8

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.

KW - GWAS

KW - Gene

KW - HDL-C

KW - IBC-array

KW - LDL-C

KW - Lipids

KW - Meta-analysis

KW - Pakistan

KW - Population structure

KW - Triglyceride

UR - http://www.scopus.com/inward/record.url?scp=78649259262&partnerID=8YFLogxK

U2 - 10.1161/CIRCGENETICS.109.906180

DO - 10.1161/CIRCGENETICS.109.906180

M3 - Article

C2 - 20570915

AN - SCOPUS:78649259262

SN - 1942-325X

VL - 3

SP - 348

EP - 357

JO - Circulation: Cardiovascular Genetics

JF - Circulation: Cardiovascular Genetics

IS - 4

ER -

Genetic determinants of major blood lipids in pakistanis compared with Europeans

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Keywords

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