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

Yi Cheng Chang, Yen Feng Chiu, Chih Tsueng He, Wayne Huey Herng Sheu, Ming Wei Lin, Todd B. Seto, Themistocles Assimes, Yuh Shan Jou, Lynn Su, Wei Jei Lee, Po Chu Lee, Shu Huei Tsai, Lee Ming Chuang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 31cM (logarithm of odds=3.04) with 1-logarithm of odds support interval at 24 to 34cM. 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= 7.1-10-4) blood pressure and high-density lipoprotein cholesterol (P=1.4-10-4). 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.

Original languageEnglish
Article numbere5174
JournalMedicine (United States)
Volume95
Issue number44
DOIs
StatePublished - 2016

Keywords

  • Adiponectin
  • Chinese
  • Genome-wide
  • RYR3
  • SAPPHIRe

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