Genome-wide association study of morbid obesity in Han Chinese

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/m²) 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 (p-value = 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.