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Association of common genetic variants with lipid traits in the Indian population

Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabo...

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Published in:PloS one 2014-07, Vol.9 (7), p.e101688-e101688
Main Authors: Walia, Gagandeep Kaur, Gupta, Vipin, Aggarwal, Aastha, Asghar, Mohammad, Dudbridge, Frank, Timpson, Nicholas, Singh, Nongmaithem Suraj, Kumar, M Ravi, Kinra, Sanjay, Prabhakaran, Dorairaj, Reddy, K Srinath, Chandak, Giriraj Ratan, Smith, George Davey, Ebrahim, Shah
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container_end_page e101688
container_issue 7
container_start_page e101688
container_title PloS one
container_volume 9
creator Walia, Gagandeep Kaur
Gupta, Vipin
Aggarwal, Aastha
Asghar, Mohammad
Dudbridge, Frank
Timpson, Nicholas
Singh, Nongmaithem Suraj
Kumar, M Ravi
Kinra, Sanjay
Prabhakaran, Dorairaj
Reddy, K Srinath
Chandak, Giriraj Ratan
Smith, George Davey
Ebrahim, Shah
description Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.
doi_str_mv 10.1371/journal.pone.0101688
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Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>ProQuest Biological Science Journals</collection><collection>ProQuest Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walia, Gagandeep Kaur</au><au>Gupta, Vipin</au><au>Aggarwal, Aastha</au><au>Asghar, Mohammad</au><au>Dudbridge, Frank</au><au>Timpson, Nicholas</au><au>Singh, Nongmaithem Suraj</au><au>Kumar, M Ravi</au><au>Kinra, Sanjay</au><au>Prabhakaran, Dorairaj</au><au>Reddy, K Srinath</au><au>Chandak, Giriraj Ratan</au><au>Smith, George Davey</au><au>Ebrahim, Shah</au><au>Prokunina-Olsson, Ludmila</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of common genetic variants with lipid traits in the Indian population</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-07-03</date><risdate>2014</risdate><volume>9</volume><issue>7</issue><spage>e101688</spage><epage>e101688</epage><pages>e101688-e101688</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Genome-wide association studies (GWAS) have been instrumental in identifying novel genetic variants associated with altered plasma lipid levels. However, these quantitative trait loci have not been tested in the Indian population, where there is a poorly understood and growing burden of cardiometabolic disorders. We present the association of six single nucleotide polymorphisms in 1671 sib pairs (3342 subjects) with four lipid traits: total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). We also investigated the interaction effects of gender, location, fat intake and physical activity. Each copy of the risk allele of rs964184 at APOA1 was associated with 1.06 mmol/l increase in triglycerides (SE = 0.049; p = 0.006), rs3764261 at CETP with 1.02 mmol/l increase in both total cholesterol (SE = 0.042; p = 0.017) and HDL-C (SE = 0.041; p = 0.008), rs646776 at CELSR2-PSRC1-SORT1 with 0.96 mmol/l decrease in cholesterol (SE = 0.043; p = 0.0003) and 0.15 mmol/l decrease in LDL-C levels (SE = 0.043; p = 0.0003) and rs2954029 at TRIB1 with 1.02 mmol/l increase in HDL-C (SE = 0.039; p = 0.047). A combined risk score of APOA1 and CETP loci predicted an increase of 1.25 mmol/l in HDL-C level (SE = 0.312; p = 0.0007). Urban location and sex had strong interaction effects on the genetic association of most of the studied loci with lipid traits. To conclude, we validated four genetic variants (identified by GWAS in western populations) associated with lipid traits in the Indian population. The interaction effects found here may explain the sex-specific differences in lipid levels and their heritability. Urbanization appears to influence the nature of the association with GWAS lipid loci in this population. However, these findings will require replication in other Indian populations.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24991929</pmid><doi>10.1371/journal.pone.0101688</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
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issn 1932-6203
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language eng
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source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central(OpenAccess)
subjects Adult
Biology and Life Sciences
Cardiovascular disease
Cholesterol
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Chromosomes
Chronic illnesses
Exercise
Female
Gender
Genetic diversity
Genetic variance
Genome-Wide Association Study - methods
Genomes
Genomics
Heritability
High density lipoprotein
Humans
India - ethnology
Lipid Metabolism
Lipids
Loci
Low density lipoprotein
Low density lipoproteins
Male
Middle Aged
Physical activity
Polymorphism, Single Nucleotide
Population studies
Populations
Quantitative genetics
Quantitative Trait Loci
Sex
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Strong interactions (field theory)
Triglycerides
Triglycerides - blood
Urban areas
Urban Population
Urbanization
Whites - genetics
Young Adult
title Association of common genetic variants with lipid traits in the Indian population
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