Adiponectin Concentrations: A Genome-wide Association Study

• Published in: American journal of human genetics Vol. 87; no. 4; pp. 545 - 552
• Main Authors: Jee, Sun Ha, Sull, Jae Woong, Lee, Jong-Eun, Shin, Chol, Park, Jongkeun, Kimm, Heejin, Cho, Eun-Young, Shin, Eun-Soon, Yun, Ji Eun, Park, Ji Wan, Kim, Sang Yeun, Lee, Sun Ju, Jee, Eun Jung, Baik, Inkyung, Kao, Linda, Yoon, Sungjoo Kim, Jang, Yangsoo, Beaty, Terri H.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 08.10.2010; Cell Press; Elsevier
• Subjects: 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; South Korea; Human; Genetics; Association; Concentration; Genome
• ISSN: 0002-9297; 1537-6605; 1537-6605
• DOI: 10.1016/j.ajhg.2010.09.004

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.