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. 2022 Jan 20;18(1):e1009952.
doi: 10.1371/journal.pgen.1009952. eCollection 2022 Jan.

Genome-wide association study identifies genetic risk loci for adiposity in a Taiwanese population

Henry Sung-Ching Wong  1 , Szu-Yi Tsai  1 , Hou-Wei Chu  2 , Min-Rou Lin  1 , Gan-Hong Lin  3 , Yu-Ting Tai  4 , Chen-Yang Shen  2   3   5 , Wei-Chiao Chang  1   3   6   7
Affiliations

Genome-wide association study identifies genetic risk loci for adiposity in a Taiwanese population

Henry Sung-Ching Wong et al. PLoS Genet. .

Abstract

Overweight and obese are risk factors for various diseases. In Taiwan, the combined prevalence of overweight and obesity has increased dramatically. Here, we conducted a genome-wide association study (GWAS) on four adiposity traits, including body-mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-hip ratio (WHR), using the data for more than 21,000 subjects in Taiwan Biobank. Associations were evaluated between 6,546,460 single-nucleotide polymorphisms (SNPs) and adiposity traits, yielding 13 genome-wide significant (GWS) adiposity-associated trait-loci pairs. A known gene, FTO, as well as two BF%-associated loci (GNPDA2-GABRG1 [4p12] and RNU6-2-PIAS1 [15q23]) were identified as pleiotropic effects. Moreover, RALGAPA1 was found as a specific genetic predisposing factor to high BMI in a Taiwanese population. Compared to other populations, a slightly lower heritability of the four adiposity traits was found in our cohort. Surprisingly, we uncovered the importance of neural pathways that might influence BF%, WC and WHR in the Taiwanese (East Asian) population. Additionally, a moderate genetic correlation between the WHR and BMI (γg = 0.52; p = 2.37×10-9) was detected, suggesting different genetic determinants exist for abdominal adiposity and overall adiposity. In conclusion, the obesity-related genetic loci identified here provide new insights into the genetic underpinnings of adiposity in the Taiwanese population.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Manhattan plots of adiposity phenotypes.
Genetic association results of the body-mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-hip ratio (WHR) in a Taiwanese population. Red and blue lines respectively represent genome-wide sequence significance (GWS; p = 5×10−8) and suggested significance (p = 1×10−6).
Fig 2
Fig 2. A novel gene, RALGAPA1, identified by comparison of Taiwan Biobank (TWB), GERA and Japan Biobank (BBJ) genome-wide association studies (GWASs).
The X-axis represents the position of loci (hg19). The Y-axis represents -log10(p). Red dots are p values of variants from the TWB. Green dots are p values from the BBJ. Blue dots are p values from GERA cohort (GERA). The blue horizontal line represents p = 1×10−5. The red horizontal line represents p = 5×10−8. The red dashed line represents the location of the gene.
Fig 3
Fig 3. Active enhancer enrichment of obesity-related variants in 10 cell type categories.
p values were obtained from 2000 permutations. The false detection rate (FDR) was obtained using the Benjamin-Hochberg method. The red line denotes an FDR of <0.05, and blue line denotes an FDR of <0.1.
See this image and copyright information in PMC

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References

    1. Mi Y-J, Zhang B, Wang H-J, Yan J, Han W, Zhao J, et al.. Prevalence and Secular Trends in Obesity Among Chinese Adults, 1991−2011. American Journal of Preventive Medicine. 2015;49(5):661–9. doi: 10.1016/j.amepre.2015.05.005 - DOI - PMC - PubMed
    1. Abarca-Gómez L, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Acuin C, et al.. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. The Lancet. 2017;390(10113):2627–42. doi: 10.1016/s0140-6736(17)32129-3 - DOI - PMC - PubMed
    1. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. The Lancet. 2016;387(10026):1377–96. doi: 10.1016/S0140-6736(16)30054-X - DOI - PMC - PubMed
    1. Chang HC, Yang HC, Chang HY, Yeh CJ, Chen HH, Huang KC, et al.. Morbid obesity in Taiwan: Prevalence, trends, associated social demographics, and lifestyle factors. PLoS One. 2017;12(2):e0169577. Epub 2017/02/06. doi: 10.1371/journal.pone.0169577 ; PubMed Central PMCID: PMC5289420. - DOI - PMC - PubMed
    1. Czernichow S, Kengne AP, Stamatakis E, Hamer M, Batty GD. Body mass index, waist circumference and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk?: evidence from an individual-participant meta-analysis of 82 864 participants from nine cohort studies. Obes Rev. 2011;12(9):680–7. Epub 2011/04/28. doi: 10.1111/j.1467-789X.2011.00879.x ; PubMed Central PMCID: PMC4170776. - DOI - PMC - PubMed

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