A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)
Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we re...
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| Veröffentlicht in: | PloS one 2015-11, Vol.10 (11), p.e0134649-e0134649 |
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| creator | Gao, Chuan Wang, Nan Guo, Xiuqing Ziegler, Julie T Taylor, Kent D Xiang, Anny H Hai, Yang Kridel, Steven J Nadler, Jerry L Kandeel, Fouad Raffel, Leslie J Chen, Yii-Der I Norris, Jill M Rotter, Jerome I Watanabe, Richard M Wagenknecht, Lynne E Bowden, Donald W Speliotes, Elizabeth K Goodarzi, Mark O Langefeld, Carl D Palmer, Nicholette D |
| description | Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P |
| doi_str_mv | 10.1371/journal.pone.0134649 |
| format | Article |
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Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P<5.00x10-8) in IRASFS. A missense SNP in the isocitrate dehydrogenase 1 gene (IDH1) was associated with WAIST (rs34218846, MAF = 6.8%, PDOM = 1.62x10-8). This protein is postulated to play an important role in fat and cholesterol biosynthesis as demonstrated in cell and knock-out animal models. Four correlated intronic SNPs in the Zinc finger, GRF-type containing 1 gene (ZGRF1; SNP rs1471880, MAF = 48.1%, PDOM = 1.00x10-8) were strongly associated with WHR. The exact biological function of ZGRF1 and the connection with adiposity remains unclear. SNPs with p-values less than 5.00x10-6 from IRASFS were selected for replication. Meta-analysis was computed across seven independent Hispanic-American cohorts (nmax = 4156) and the strongest signal was rs1471880 (PDOM = 8.38x10-6) in ZGRF1 with WAIST. In conclusion, a genome-wide and exome chip association study was conducted that identified two novel loci (IDH1 and ZGRF1) associated with adiposity. While replication efforts were inconclusive, when taken together with the known biology, IDH1 and ZGRF1 warrant further evaluation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0134649</identifier><identifier>PMID: 26599207</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipose tissue ; Adiposity - genetics ; Adults ; Analysis ; Animal models ; Arteriosclerosis ; Atherosclerosis ; Biochemistry ; Bioinformatics ; Biomedical research ; Biophysics ; Biosynthesis ; Body fat ; Body mass ; Body mass index ; Body size ; Cancer ; Cardiovascular disease ; Cell culture ; Cholesterol ; Dehydrogenases ; Diabetes ; Epidemics ; Family studies ; Gene expression ; Genetic aspects ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genomes ; Genomics ; Health care ; Hip ; Hispanic Americans ; Hispanic Americans - genetics ; Hispanic people ; Humans ; Insulin ; Internal medicine ; Isocitrate dehydrogenase ; Isocitrate Dehydrogenase - genetics ; Loci ; Membrane Proteins - genetics ; Meta-analysis ; Metabolic disorders ; Mutation ; Obesity ; Obesity - genetics ; Pediatrics ; Physiological aspects ; Physiology ; Polymorphism, Single Nucleotide ; Population ; Preventive medicine ; Public health ; Replication ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Zinc ; Zinc finger proteins</subject><ispartof>PloS one, 2015-11, Vol.10 (11), p.e0134649-e0134649</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Gao et al 2015 Gao et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-adfc12f312b68f33664587396701b1e6f5036dac8a405dd48d0c7381dbfacc63</citedby><cites>FETCH-LOGICAL-c692t-adfc12f312b68f33664587396701b1e6f5036dac8a405dd48d0c7381dbfacc63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658008/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658008/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26599207$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Chuan</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>Guo, Xiuqing</creatorcontrib><creatorcontrib>Ziegler, Julie T</creatorcontrib><creatorcontrib>Taylor, Kent D</creatorcontrib><creatorcontrib>Xiang, Anny H</creatorcontrib><creatorcontrib>Hai, Yang</creatorcontrib><creatorcontrib>Kridel, Steven J</creatorcontrib><creatorcontrib>Nadler, Jerry L</creatorcontrib><creatorcontrib>Kandeel, Fouad</creatorcontrib><creatorcontrib>Raffel, Leslie J</creatorcontrib><creatorcontrib>Chen, Yii-Der I</creatorcontrib><creatorcontrib>Norris, Jill M</creatorcontrib><creatorcontrib>Rotter, Jerome I</creatorcontrib><creatorcontrib>Watanabe, Richard M</creatorcontrib><creatorcontrib>Wagenknecht, Lynne E</creatorcontrib><creatorcontrib>Bowden, Donald W</creatorcontrib><creatorcontrib>Speliotes, Elizabeth K</creatorcontrib><creatorcontrib>Goodarzi, Mark O</creatorcontrib><creatorcontrib>Langefeld, Carl D</creatorcontrib><creatorcontrib>Palmer, Nicholette D</creatorcontrib><title>A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P<5.00x10-8) in IRASFS. A missense SNP in the isocitrate dehydrogenase 1 gene (IDH1) was associated with WAIST (rs34218846, MAF = 6.8%, PDOM = 1.62x10-8). This protein is postulated to play an important role in fat and cholesterol biosynthesis as demonstrated in cell and knock-out animal models. Four correlated intronic SNPs in the Zinc finger, GRF-type containing 1 gene (ZGRF1; SNP rs1471880, MAF = 48.1%, PDOM = 1.00x10-8) were strongly associated with WHR. The exact biological function of ZGRF1 and the connection with adiposity remains unclear. SNPs with p-values less than 5.00x10-6 from IRASFS were selected for replication. Meta-analysis was computed across seven independent Hispanic-American cohorts (nmax = 4156) and the strongest signal was rs1471880 (PDOM = 8.38x10-6) in ZGRF1 with WAIST. In conclusion, a genome-wide and exome chip association study was conducted that identified two novel loci (IDH1 and ZGRF1) associated with adiposity. While replication efforts were inconclusive, when taken together with the known biology, IDH1 and ZGRF1 warrant further evaluation.</description><subject>Adipose tissue</subject><subject>Adiposity - genetics</subject><subject>Adults</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical research</subject><subject>Biophysics</subject><subject>Biosynthesis</subject><subject>Body fat</subject><subject>Body mass</subject><subject>Body mass index</subject><subject>Body size</subject><subject>Cancer</subject><subject>Cardiovascular disease</subject><subject>Cell culture</subject><subject>Cholesterol</subject><subject>Dehydrogenases</subject><subject>Diabetes</subject><subject>Epidemics</subject><subject>Family studies</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health care</subject><subject>Hip</subject><subject>Hispanic Americans</subject><subject>Hispanic Americans - genetics</subject><subject>Hispanic people</subject><subject>Humans</subject><subject>Insulin</subject><subject>Internal medicine</subject><subject>Isocitrate dehydrogenase</subject><subject>Isocitrate Dehydrogenase - genetics</subject><subject>Loci</subject><subject>Membrane Proteins - genetics</subject><subject>Meta-analysis</subject><subject>Metabolic disorders</subject><subject>Mutation</subject><subject>Obesity</subject><subject>Obesity - genetics</subject><subject>Pediatrics</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Preventive medicine</subject><subject>Public health</subject><subject>Replication</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Zinc</subject><subject>Zinc finger 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Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)</title><author>Gao, Chuan ; Wang, Nan ; Guo, Xiuqing ; Ziegler, Julie T ; Taylor, Kent D ; Xiang, Anny H ; Hai, Yang ; Kridel, Steven J ; Nadler, Jerry L ; Kandeel, Fouad ; Raffel, Leslie J ; Chen, Yii-Der I ; Norris, Jill M ; Rotter, Jerome I ; Watanabe, Richard M ; Wagenknecht, Lynne E ; Bowden, Donald W ; Speliotes, Elizabeth K ; Goodarzi, Mark O ; Langefeld, Carl D ; Palmer, Nicholette D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-adfc12f312b68f33664587396701b1e6f5036dac8a405dd48d0c7381dbfacc63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adipose tissue</topic><topic>Adiposity - genetics</topic><topic>Adults</topic><topic>Analysis</topic><topic>Animal 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dehydrogenase</topic><topic>Isocitrate Dehydrogenase - genetics</topic><topic>Loci</topic><topic>Membrane Proteins - genetics</topic><topic>Meta-analysis</topic><topic>Metabolic disorders</topic><topic>Mutation</topic><topic>Obesity</topic><topic>Obesity - genetics</topic><topic>Pediatrics</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population</topic><topic>Preventive medicine</topic><topic>Public health</topic><topic>Replication</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Zinc</topic><topic>Zinc finger proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gao, Chuan</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>Guo, Xiuqing</creatorcontrib><creatorcontrib>Ziegler, Julie T</creatorcontrib><creatorcontrib>Taylor, Kent D</creatorcontrib><creatorcontrib>Xiang, Anny 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Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</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>Gao, Chuan</au><au>Wang, Nan</au><au>Guo, Xiuqing</au><au>Ziegler, Julie T</au><au>Taylor, Kent D</au><au>Xiang, Anny H</au><au>Hai, Yang</au><au>Kridel, Steven J</au><au>Nadler, Jerry L</au><au>Kandeel, Fouad</au><au>Raffel, Leslie J</au><au>Chen, Yii-Der I</au><au>Norris, Jill M</au><au>Rotter, Jerome I</au><au>Watanabe, Richard M</au><au>Wagenknecht, Lynne E</au><au>Bowden, Donald W</au><au>Speliotes, Elizabeth K</au><au>Goodarzi, Mark O</au><au>Langefeld, Carl D</au><au>Palmer, Nicholette D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-11-24</date><risdate>2015</risdate><volume>10</volume><issue>11</issue><spage>e0134649</spage><epage>e0134649</epage><pages>e0134649-e0134649</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P<5.00x10-8) in IRASFS. A missense SNP in the isocitrate dehydrogenase 1 gene (IDH1) was associated with WAIST (rs34218846, MAF = 6.8%, PDOM = 1.62x10-8). This protein is postulated to play an important role in fat and cholesterol biosynthesis as demonstrated in cell and knock-out animal models. Four correlated intronic SNPs in the Zinc finger, GRF-type containing 1 gene (ZGRF1; SNP rs1471880, MAF = 48.1%, PDOM = 1.00x10-8) were strongly associated with WHR. The exact biological function of ZGRF1 and the connection with adiposity remains unclear. SNPs with p-values less than 5.00x10-6 from IRASFS were selected for replication. Meta-analysis was computed across seven independent Hispanic-American cohorts (nmax = 4156) and the strongest signal was rs1471880 (PDOM = 8.38x10-6) in ZGRF1 with WAIST. In conclusion, a genome-wide and exome chip association study was conducted that identified two novel loci (IDH1 and ZGRF1) associated with adiposity. While replication efforts were inconclusive, when taken together with the known biology, IDH1 and ZGRF1 warrant further evaluation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26599207</pmid><doi>10.1371/journal.pone.0134649</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-11, Vol.10 (11), p.e0134649-e0134649 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1735911346 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adipose tissue Adiposity - genetics Adults Analysis Animal models Arteriosclerosis Atherosclerosis Biochemistry Bioinformatics Biomedical research Biophysics Biosynthesis Body fat Body mass Body mass index Body size Cancer Cardiovascular disease Cell culture Cholesterol Dehydrogenases Diabetes Epidemics Family studies Gene expression Genetic aspects Genetic Association Studies Genetic Predisposition to Disease Genomes Genomics Health care Hip Hispanic Americans Hispanic Americans - genetics Hispanic people Humans Insulin Internal medicine Isocitrate dehydrogenase Isocitrate Dehydrogenase - genetics Loci Membrane Proteins - genetics Meta-analysis Metabolic disorders Mutation Obesity Obesity - genetics Pediatrics Physiological aspects Physiology Polymorphism, Single Nucleotide Population Preventive medicine Public health Replication Single nucleotide polymorphisms Single-nucleotide polymorphism Zinc Zinc finger proteins |
| title | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS) |
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