Adiponectin Concentrations: A Genome-wide Association Study
Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a t...
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| Published in | American journal of human genetics Vol. 87; no. 4; pp. 545 - 552 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Cambridge, MA
Elsevier Inc
08.10.2010
Cell Press Elsevier |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10−15 in the initial sample, p = 6.58 × 10−39 in the second genome-wide sample, and p = 2.12 × 10−32 in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10−83. The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10−58) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. |
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| AbstractList | Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 X 10^-15 in the initial sample, p = 6.58 x 10^-39 in the second genome-wide sample, and p = 2.12 x 10^-32 in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 x 10^-83. The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 x 10^-58) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. [PUBLICATION ABSTRACT] Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10 −15 in the initial sample, p = 6.58 × 10 −39 in the second genome-wide sample, and p = 2.12 × 10 −32 in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10 −83 . The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10 −58 ) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10−15 in the initial sample, p = 6.58 × 10−39 in the second genome-wide sample, and p = 2.12 × 10−32 in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10−83. The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10−58) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 x 10 super(-15) in the initial sample, p = 6.58 x 10 super(-39) in the second genome-wide sample, and p = 2.12 x 10 super(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 x 10 super(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 x 10 super(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults. |
| Author | Lee, Sun Ju Kimm, Heejin Kao, Linda Jee, Eun Jung Shin, Eun-Soon Lee, Jong-Eun Kim, Sang Yeun Shin, Chol Yoon, Sungjoo Kim Yun, Ji Eun Park, Ji Wan Sull, Jae Woong Jang, Yangsoo Beaty, Terri H. Cho, Eun-Young Jee, Sun Ha Park, Jongkeun Baik, Inkyung |
| AuthorAffiliation | 8 Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon 200-702, South Korea 7 Department of Biomedical Sciences, The Catholic University of Korea, Seoul 137-701, South Korea 5 Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, South Korea 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA 9 Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul 136-702, South Korea 4 DNA Link, Inc., Seoul 121-850, South Korea 10 Cardiology Division and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 102-752, South Korea 3 Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam 461-713, South Korea 6 Research Institute of Molecular Genetics, The Catholic University of Korea, Seoul 137-701, South Korea 1 Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate S |
| AuthorAffiliation_xml | – name: 6 Research Institute of Molecular Genetics, The Catholic University of Korea, Seoul 137-701, South Korea – name: 10 Cardiology Division and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 102-752, South Korea – name: 1 Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – name: 7 Department of Biomedical Sciences, The Catholic University of Korea, Seoul 137-701, South Korea – name: 8 Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon 200-702, South Korea – name: 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA – name: 9 Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul 136-702, South Korea – name: 4 DNA Link, Inc., Seoul 121-850, South Korea – name: 5 Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, South Korea – name: 3 Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam 461-713, South Korea |
| Author_xml | – sequence: 1 givenname: Sun Ha surname: Jee fullname: Jee, Sun Ha email: jsunha@yuhs.ac organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 2 givenname: Jae Woong surname: Sull fullname: Sull, Jae Woong organization: Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam 461-713, South Korea – sequence: 3 givenname: Jong-Eun surname: Lee fullname: Lee, Jong-Eun organization: DNA Link, Inc., Seoul 121-850, South Korea – sequence: 4 givenname: Chol surname: Shin fullname: Shin, Chol organization: Department of Internal Medicine, Korea University Ansan Hospital, Ansan 425-707, South Korea – sequence: 5 givenname: Jongkeun surname: Park fullname: Park, Jongkeun organization: Research Institute of Molecular Genetics, The Catholic University of Korea, Seoul 137-701, South Korea – sequence: 6 givenname: Heejin surname: Kimm fullname: Kimm, Heejin organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 7 givenname: Eun-Young surname: Cho fullname: Cho, Eun-Young organization: DNA Link, Inc., Seoul 121-850, South Korea – sequence: 8 givenname: Eun-Soon surname: Shin fullname: Shin, Eun-Soon organization: DNA Link, Inc., Seoul 121-850, South Korea – sequence: 9 givenname: Ji Eun surname: Yun fullname: Yun, Ji Eun organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 10 givenname: Ji Wan surname: Park fullname: Park, Ji Wan organization: Department of Medical Genetics, College of Medicine, Hallym University, Chuncheon 200-702, South Korea – sequence: 11 givenname: Sang Yeun surname: Kim fullname: Kim, Sang Yeun organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 12 givenname: Sun Ju surname: Lee fullname: Lee, Sun Ju organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 13 givenname: Eun Jung surname: Jee fullname: Jee, Eun Jung organization: Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 102-752, South Korea – sequence: 14 givenname: Inkyung surname: Baik fullname: Baik, Inkyung organization: Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul 136-702, South Korea – sequence: 15 givenname: Linda surname: Kao fullname: Kao, Linda organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA – sequence: 16 givenname: Sungjoo Kim surname: Yoon fullname: Yoon, Sungjoo Kim organization: Research Institute of Molecular Genetics, The Catholic University of Korea, Seoul 137-701, South Korea – sequence: 17 givenname: Yangsoo surname: Jang fullname: Jang, Yangsoo email: jangys1212@yuhs.ac organization: Cardiology Division and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 102-752, South Korea – sequence: 18 givenname: Terri H. surname: Beaty fullname: Beaty, Terri H. organization: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA |
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| Copyright | 2010 The American Society of Human Genetics 2015 INIST-CNRS Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. Copyright Cell Press Oct 8, 2010 2010 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. 2010 The American Society of Human Genetics |
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| SubjectTerms | Adiponectin - blood Adult Asian people Asian People - genetics Biological and medical sciences Blood Pressure Body Mass Index Cadherins - genetics Cell Line Cholesterol - blood Chromosomes DNA Primers - genetics Female Fundamental and applied biological sciences. Psychology Gene expression General aspects. Genetic counseling Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genomics Genotype Genotype & phenotype Humans Linkage Disequilibrium Male Medical genetics Medical sciences Meta-analysis Middle Aged Molecular and cellular biology Polymorphism, Single Nucleotide - genetics Promoter Regions, Genetic - genetics Proteins Sequence Analysis, DNA |
| Title | Adiponectin Concentrations: A Genome-wide Association Study |
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