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Effect of interaction between obesity-promoting genetic variants and behavioral factors on the risk of obese phenotypes

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Abstract

The studies investigating gene–gene and gene–environment (or gene–behavior) interactions provide valuable insight into the pathomechanisms underlying obese phenotypes. The Pakistani population due to its unique characteristics offers numerous advantages for conducting such studies. In this view, the current study was undertaken to examine the effects of gene–gene and gene–environment/behavior interactions on the risk of obesity in a sample of Pakistani population. A total of 578 adult participants including 290 overweight/obese cases and 288 normal-weight controls were involved. The five key obesity-associated genetic variants namely MC4R rs17782313, BDNF rs6265, FTO rs1421085, TMEM18 rs7561317, and NEGR1 rs2815752 were genotyped using the TaqMan allelic discrimination assays. The data related to behavioral factors, such as eating pattern, diet consciousness, the tendency toward fat-dense food (TFDF), sleep duration, sleep–wake cycle (SWC), shift work (SW), and physical activity levels were collected via a questionnaire. Gene–gene and gene–behavior interactions were analyzed by multifactor dimensionality reduction and linear regression, respectively. In our study, only TMEM18 rs7561317 was found to be significantly associated with anthropometric traits with no significant effect of gene–gene interactions were observed on obesity-related phenotypes. However, the genetic variants were found to interact with the behavioral factors to significantly influence various obesity-related anthropometric traits including BMI, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and percentage of body fat. In conclusion, the interaction between genetic architecture and behavior/environment determines the outcome of obesity-related anthropometric phenotypes. Thus, gene–environment/behavior interaction studies should be promoted to explore the risk of complex and multifactorial disorders, such as obesity.

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Acknowledgements

We are grateful to all participants for their participation in the current study. We also thank Ms. Maha Mobin, Mr. Saad Mirza, and Ms. Soma Rehmani for their contribution to data collection.

Funding

The work was funded by a research grant from the Higher Education Commission (HEC) of Pakistan (Ref. No. 5740/Sindh/NRPU/R&D/HEC/2016), and a recurring grant from the International Center for Chemical and Biological Sciences (ICCBS). The funding bodies did not participate in the study design, sample collection, data analysis and interpretation, and manuscript writing.

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  1. Molecular Biology and Human Genetics Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan

    Sobia Rana, Ayesha Sultana & Adil Anwar Bhatti

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  1. Sobia Rana
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  2. Ayesha Sultana
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  3. Adil Anwar Bhatti
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Contributions

SR conceptualized and supervised the work, acquired funding, contributed to data collection, analysis, and interpretation of the data, and critically revised the manuscript. AS and AAB performed the experiments, contributed to data collection, analysis, and interpretation of the data, and wrote the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sobia Rana.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in the study involving human participants were per the ethical standards of the Independent Ethics Committee (IEC) of the ICCBS and Advanced Studies and Research Board (ASRB) of the University of Karachi, Pakistan, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the IEC of the ICCBS and ASRB of the University of Karachi.

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Written informed consent was obtained from all individual participants included in the study.

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Communicated by Stefan Hohmann.

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Rana, S., Sultana, A. & Bhatti, A.A. Effect of interaction between obesity-promoting genetic variants and behavioral factors on the risk of obese phenotypes. Mol Genet Genomics 296, 919–938 (2021). https://doi.org/10.1007/s00438-021-01793-y

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