title: Genome-wide linkage analysis and regional fine mapping identified variants in the RYR3 gene as a novel quantitative trait locus for circulating adiponectin in Chinese population.
abstract: Adiponectin is adipocyte-secreted cytokine with potent insulin-sensitizing action in peripheral tissues. The heritability of plasma adiponectin is high in Han Chinese population.To identify genetic loci influencing plasma adiponectin levels in Chinese population, we performed a genome-wide linkage scan in 1949 Chinese participants of the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance family study and mapped a quantitative trail locus located on chromosome 15 at 31 cM (logarithm of odds = 3.04) with 1-logarithm of odds support interval at 24 to 34 cM. Within this mapped region, we further genotyped a total of 68 single-nucleotide polymorphisms in 12 genes. Association analysis revealed that haplotypes composed of single-nucleotide polymorphisms in the ryanodine receptor 3 (RYR3) gene had strongest association with plasma adiponectin. RYR3 haplotypes were also associated with systolic (P = 0.001) and diastolic (P = 7.1 × 10) blood pressure and high-density lipoprotein cholesterol (P = 1.4 × 10). Furthermore, an inverse relationship between expression of RYR3 and adiponectin was observed in human abdominal adipose tissue. In conclusion, a genome-wide linkage scan and regional association fine-mapping identified variants in the RYR3 gene as a quantitative trail locus for plasma adiponectin levels in Chinese population.
authors.affiliation: Graduate Institute of Medical Genomics and Proteomics, National Taiwan University Department of Internal Medicine, National Taiwan University Hospital Institute of Biomedical Science, Academia Sinica, Taipei Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, Taipei Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung Institute of Public Health, National Yang-Ming University, Taipei, Taiwan Center for Outcomes Research and Evaluation, Non-Invasive Cardiology Laboratory, The Queen's Medical Center, Honolulu, HI Department of Medicine, Stanford University School of Medicine, Stanford, CA Graduate Institute of Molecular Medicine, National Taiwan University, Taipei Department of Surgery, Ming-Sheng General Hospital, Taoyuan Department of General Surgery, National Taiwan University Hospital Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Yen-Feng
authors.initials: YF
authors.lastname: Chiu
authors.forename: Chih-Tsueng
authors.initials: CT
authors.lastname: He
authors.forename: Wayne Huey-Herng
authors.initials: WH
authors.lastname: Sheu
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Todd B
authors.initials: TB
authors.lastname: Seto
authors.forename: Themistocles
authors.initials: T
authors.lastname: Assimes
authors.forename: Yuh-Shan
authors.initials: YS
authors.lastname: Jou
authors.forename: Lynn
authors.initials: L
authors.lastname: Su
authors.forename: Wei-Jei
authors.initials: WJ
authors.lastname: Lee
authors.forename: Po-Chu
authors.initials: PC
authors.lastname: Lee
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Tsai
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D019837:Ryanodine Receptor Calcium Release Channel