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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4658008?pdf=render |
| _version_ | 1818322030788870144 |
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| author | Chuan Gao Nan Wang Xiuqing Guo Julie T Ziegler Kent D Taylor Anny H Xiang Yang Hai Steven J Kridel Jerry L Nadler Fouad Kandeel Leslie J Raffel Yii-Der I Chen Jill M Norris Jerome I Rotter Richard M Watanabe Lynne E Wagenknecht Donald W Bowden Elizabeth K Speliotes Mark O Goodarzi Carl D Langefeld Nicholette D Palmer |
| author_facet | Chuan Gao Nan Wang Xiuqing Guo Julie T Ziegler Kent D Taylor Anny H Xiang Yang Hai Steven J Kridel Jerry L Nadler Fouad Kandeel Leslie J Raffel Yii-Der I Chen Jill M Norris Jerome I Rotter Richard M Watanabe Lynne E Wagenknecht Donald W Bowden Elizabeth K Speliotes Mark O Goodarzi Carl D Langefeld Nicholette D Palmer |
| author_sort | Chuan Gao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T10:50:19Z |
| format | Article |
| id | doaj.art-46ee037fe6bb4cd9a6d303698c6c7525 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:50:19Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-46ee037fe6bb4cd9a6d303698c6c75252022-12-21T23:49:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e013464910.1371/journal.pone.0134649A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS).Chuan GaoNan WangXiuqing GuoJulie T ZieglerKent D TaylorAnny H XiangYang HaiSteven J KridelJerry L NadlerFouad KandeelLeslie J RaffelYii-Der I ChenJill M NorrisJerome I RotterRichard M WatanabeLynne E WagenknechtDonald W BowdenElizabeth K SpeliotesMark O GoodarziCarl D LangefeldNicholette D PalmerObesity 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.http://europepmc.org/articles/PMC4658008?pdf=render |
| spellingShingle | Chuan Gao Nan Wang Xiuqing Guo Julie T Ziegler Kent D Taylor Anny H Xiang Yang Hai Steven J Kridel Jerry L Nadler Fouad Kandeel Leslie J Raffel Yii-Der I Chen Jill M Norris Jerome I Rotter Richard M Watanabe Lynne E Wagenknecht Donald W Bowden Elizabeth K Speliotes Mark O Goodarzi Carl D Langefeld Nicholette D Palmer A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). PLoS ONE |
| title | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). |
| title_full | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). |
| title_fullStr | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). |
| title_full_unstemmed | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). |
| title_short | A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS). |
| title_sort | comprehensive analysis of common and rare variants to identify adiposity loci in hispanic americans the iras family study irasfs |
| url | http://europepmc.org/articles/PMC4658008?pdf=render |
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