Genome-wide association study of morbid obesity in Han Chinese

Abstract

Background: As obesity is becoming pandemic, morbid obesity (MO), an extreme type of obesity, is an emerging issue worldwide. It is imperative to understand the factors responsible for huge weight gain in certain populations in the modern society. Very few genome-wide association studies (GWAS) have been conducted on MO patients. This study is the first MO-GWAS study in the Han-Chinese population in Asia. Methods: We conducted a two-stage GWAS with 1110 MO bariatric patients (body mass index [BMI] ≥ 35 kg/m 2) from Min-Sheng General Hospital, Taiwan. The first stage involved 575 patients, and 1729 sex-and age-matched controls from the Taiwan Han Chinese Cell and Genome Bank. In the second stage, another 535 patients from the same hospital were genotyped for 52 single nucleotide polymorphisms (SNPs) discovered in the first stage, and 9145 matched controls from Taiwan Biobank were matched for confirmation analysis. Results: The results of the joint analysis for the second stage revealed six top ranking SNPs, including rs8050136 (pvalue = 7.80 × 10 − 10), rs9939609 (p-value = 1.32 × 10 − 9), rs1421085 (p-value = 1.54 × 10 − 8), rs9941349 (p-value = 9.05 × 10 − 8), rs1121980 (p-value = 7.27 × 10 − 7), and rs9937354 (p-value = 6.65 × 10 − 7), which were all located in FTO gene. Significant associations were also observed between MO and RBFOX1, RP11-638 L3.1, TMTC1, CBLN4, CSMD3, and ERBB4, respectively, using the Bonferroni correction criteria for 52 SNPs (p < 9.6 × 10 − 4). Conclusion: The most significantly associated locus of MO in the Han-Chinese population was the well-known FTO gene. These SNPs located in intron 1, may include the leptin receptor modulator. Other significant loci, showing weak associations with MO, also suggested the potential mechanism underlying the disorders with eating behaviors or brain/neural development.

Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites

“…TMTC2 interactions with certain miRNAs hint towards a role in Parkinson’s disease [ 15 ]. GWAS associates TMTC2 with obesity in Caribean Hispanics [ 16 ] and Han Chinese [ 17 ], left ventricular mass increase [ 16 ] as well as with immune conditions such as eczema, asthma and ‘atopic march’ [ 18 ]. Family studies show TMTC3 mutations being causative for cobblestone lissencephaly [ 19 ] and periventricular nodular heterotopia with intellectual disability and epilepsy [ 20 ].…”

Race/ethnicity-associated blood DNA methylation differences between Japanese and European American women: an exploratory study

“…CSMD3 is considered a driver gene in liver cancer [60]. Although the biological function of CSMD3 has not been fully understood, this gene is associated with alcohol exposure [61] and its genetic alteration is associated with morbid obesity [62]. SH3BP4 is a potential tumor suppressor, and its methylation is related to impaired insulin signaling [63].…”

Omics Approaches in Adipose Tissue and Skeletal Muscle Addressing the Role of Extracellular Matrix in Obesity and Metabolic Dysfunction

“…These proteins are the main ECM component in adipose tissue and their excessive accumulation in obesity is the main cause of tissue fibrosis, rigidity, and finally insulin resistance. A total of 12 GWAS-reported loci were grouped into this category after the search ( ADIPOQ , APOE , CBLN4 , COL4A1 , COL6A5 , CTSS , F12 , F13A1 , FRAS1 , ITIH4 , SGCZ, and SSPN ) [ 64 , 65 , 66 , 69 , 70 , 71 , 73 , 78 , 79 , 80 , 84 , 85 , 86 , 87 , 89 , 92 , 93 , 94 , 95 , 96 ]. From these, it highlights structural collagen components such as COL4A1 , COL6A5 and other types of structural ECM components such as FRAS1 , SGCZ, and SSPN , for which SNPs and CNVs have been directly associated with higher risk of obesity or increased anthropometry measurements in diverse ethnic populations (at genome-wide significance levels P < 5 × 10 e−8 ) [ 62 , 67 , 68 , 72 , 74 , 75 ].…”