Genetic determinants of major blood lipids in Pakistanis compared with Europeans.
BACKGROUND
Evidence is sparse about the genetic determinants of major lipids in Pakistanis.


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.
Saleheen
Danish
D
Center for Non-Communicable Diseases Karachi, Pakistan. danish.saleheen@cncdpk.com
Soranzo
Nicole
N
Rasheed
Asif
A
Scharnagl
Hubert
H
Gwilliam
Rhian
R
Alexander
Myriam
M
Inouye
Michael
M
Zaidi
Moazzam
M
Potter
Simon
S
Haycock
Philip
P
Bumpstead
Suzanna
S
Kaptoge
Stephen
S
Di Angelantonio
Emanuele
E
Sarwar
Nadeem
N
Hunt
Sarah E
SE
Sheikh
Nasir
N
Shah
Nabi
N
Samuel
Maria
M
Haider
Shajjia Razi
SR
Murtaza
Muhammed
M
Thompson
Alexander
A
Gobin
Reeta
R
Butterworth
Adam
A
Ahmad
Usman
U
Hakeem
Abdul
A
Zaman
Khan Shah
KS
Kundi
Assadullah
A
Yaqoob
Zia
Z
Cheema
Liaquat Ali
LA
Qamar
Nadeem
N
Faruqui
Azhar
A
Mallick
Nadeem Hayat
NH
Azhar
Muhammad
M
Samad
Abdus
A
Ishaq
Muhammad
M
Rasheed
Syed Zahed
SZ
Jooma
Rashid
R
Niazi
Jawaid Hassan
JH
Gardezi
Ali Raza
AR
Memon
Nazir Ahmed
NA
Ghaffar
Abdul
A
Rehman
Fazal-ur
FU
Hoffmann
Michael Marcus
MM
Renner
Wilfried
W
Kleber
Marcus E
ME
Grammer
Tanja B
TB
Stephens
Jonathon
J
Attwood
Anthony
A
Koch
Kerstin
K
Hussain
Mustafa
M
Kumar
Kishore
K
Saleem
Asim
A
Kumar
Kishwar
K
Daood
Muhammad Salman
MS
Gul
Aftab Alam
AA
Abbas
Shahid
S
Zafar
Junaid
J
Shahid
Faisal
F
Bhatti
Shahzad Majeed
SM
Ali
Syed Saadat
SS
Muhammad
Fahim
F
Sagoo
Gurdeep
G
Bray
Sarah
S
McGinnis
Ralph
R
Dudbridge
Frank
F
Winkelmann
Bernhard R
BR
Böehm
Bernhard
B
Thompson
Simon
S
Ouwehand
Willem
W
März
Winfried
W
Frossard
Philippe
P
Danesh
John
J
Deloukas
Panos
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005060:Europe; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000097:blood / Q000208:ethnology / Q000235:genetics; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide
D008055:Lipids