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Development of a genetic risk score for obesity predisposition evaluation

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Abstract

Obesity is a major public health issue resulting from an interaction between genetic and environmental factors. Genetic risk scores (GRSs) are useful to summarize the effects of many genetic variants on obesity risk. In this study, we aimed to assess the association of previously well-studied genetic variants with obesity and develop a genetic risk score to anticipate the risk of obesity development in the Iranian population. Among 968 participants, 599 (61.88%) were obese, and 369 (38.12%) were considered control samples. After genotyping, an initial screening of 16 variants associated with body mass index (BMI) was performed utilizing a general linear model (p < 0.25), and seven genetic variants were selected. The association of these variants with obesity was examined using a multivariate logistic regression model (p < 0.05), and finally, five variants were found to be significantly associated with obesity. Two gene score models (weighted and unweighted), including these five loci, were constructed. To compare the discriminative power of the models, the area under the curve was calculated using tenfold internal cross‐validation. Among the studied variants, ADRB3 rs4994, FTO rs9939609, ADRB2 rs1042714, IL6 rs1800795, and MTHFR rs1801133 polymorphisms were significantly associated with obesity in the Iranian population. Both of the constructed models were significantly associated with BMI (p < 0.05) and the area under the mean curve of the weighted GRS and unweighted GRS were 70.22% ± 0.05 and 70.19% ± 0.05, respectively. Both GRSs proved to predict obesity and could potentially be utilized as genetic tools to assess the obesity predisposition in the Iranian population. Also, among the studied variants, ADRB3 rs4994 and FTO rs9939609 polymorphisms have the highest impacts on the risk of obesity.

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Acknowledgements

We thank all the research staff of Dr. Zeinali’s Medical Genetics Laboratory.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Armin Soleymaniniya and Sobhan Bahrami Zadegan contributed equally to this work.

Authors and Affiliations

  1. Department of Biotechnology, College of Science, University of Tehran, Enghelab Avenue, Tehran, 14155-6455, Iran

    Narges Damavandi, Armin Soleymaniniya, Sobhan Bahrami Zadegan, Mohammad Hasan Samiee Aref & Sirous Zeinali

  2. Dr. Zeinali’s Medical Genetics Laboratory, Kawsar Human Genetics Research Center, Tehran, Iran

    Narges Damavandi, Sobhan Bahrami Zadegan, Mohammad Hasan Samiee Aref & Sirous Zeinali

  3. Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Sirous Zeinali

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  1. Narges Damavandi
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  4. Mohammad Hasan Samiee Aref
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Contributions

ND was responsible for designing the study, data collection, interpreting results, model development and writing the report. SBZ and MHSA contributed to sample analysis, data interpretation, writing the report, and created the tables. AS contributed to data analyses, model constructing and writing the report. SZ provided supervision in all the steps and writing the report.

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Correspondence to Sirous Zeinali.

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Communicated by Shuhua Xu.

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Damavandi, N., Soleymaniniya, A., Bahrami Zadegan, S. et al. Development of a genetic risk score for obesity predisposition evaluation. Mol Genet Genomics 297, 1495–1503 (2022). https://doi.org/10.1007/s00438-022-01923-0

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