Genome-wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population

BMC Genomics

Research Article

Kwan-Dun Wu¹  Wen-Jane Lee²  Hui-Ling Chen³  Yen-Feng Chiu³  Chao A. Hsiung³  Ren-Hua Chung³  Thomas Quertermous⁴  Yi-Jen Hung⁵  Ming-Wei Lin⁶  Yii-Der I. Chen⁷ 

[1] Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan;Department of Social Work, Tunghai University, Taichung, Taiwan;Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, No 35, Keyan Road, Zhunan, 350, Miaoli, Taiwan;Division of Cardiovascular Medicine and Stanford Cardiovascular Institute, Falk Cardiovascular Research Center, Stanford University, Stanford, California, USA;Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;Institute of Public Health, National Yang-Ming University School of Medicine, Taipei, Taiwan;Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, USA;

关键词: Fasting glucose;    Fasting insulin;    Copy number variations;    Family-based association analysis;   

DOI  :  10.1186/s12864-017-3975-0

 received in 2016-11-03, accepted in 2017-07-31,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundFasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin.ResultsWe conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10−4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort.ConclusionsPrevious studies have found that SNPs in SFMBT1 are associated with blood pressure and serum urate concentration, suggesting that SFMBT1 may have functional implications in some metabolic-related traits.

【 授权许可】

CC BY   
© The Author(s). 2017