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Genetics and Epigenetics

A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults

International Journal of Obesity volume 40, pages 186–190 (2016)Cite this article

Subjects

Abstract

Background:

Obesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene–lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene–lifestyle interactions in obesity.

Methods:

In the Pakistan Risk of Myocardial Infraction Study, a cross-sectional study based in Pakistan, we calculated body mass index (BMI) variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age2, sex and genetic ancestry.

Results:

The GWHVA analyses identified an intronic variant, rs140133294, in the FLJ33544 gene in association with BMI variance (P-value=3.1 × 10−8). In explicit tests of gene × lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction=0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never smokers. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction.

Conclusions:

In summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.

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Acknowledgements

We are thankful to the comments provided by John Danesh, Adam Butterworth and Robin Young at the University of Cambridge, UK. Genotyping for this study was funded by the Wellcome Trust, UK and Pfizer. Biomarker studies were supported by grants from the Fogarty International Center and the National Heart, Lung and Blood Institute. DS has received funding from the National Institutes of Health, the Fogarty International, the Wellcome Trust, the British Heart Foundation and Pfizer. Fieldwork in PROMIS was supported by funds available to investigators at the Center for Non-Communicable Diseases, Pakistan and at the University of Cambridge, UK. SA and PWF have received research and travel grants from the Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Knut and Alice Wallenberg Foundation through the Medical Faculty of Lund University, Sweden.

Author information

Author notes

  1. S Ahmad and W Zhao: These authors contributed equally to this work.

  2. P W Franks and D Saleheen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Lund University, Malmö, Sweden

    S Ahmad, F Renström, D Shungin & P W Franks

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    W Zhao & D Saleheen

  3. Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan

    A Rasheed, M Zaidi, M Samuel, N Shah, P Frossard & D Saleheen

  4. Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan

    N Shah

  5. Punjab Institute of Cardiology, Lahore, Pakistan

    N H Mallick

  6. Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden

    D Shungin & P W Franks

  7. Department of Odontology, Umeå University, Umeå, Sweden

    D Shungin

  8. National Institute of Cardiovascular Diseases, Karachi, Pakistan

    K S Zaman

  9. Karachi Institute of Heart Diseases, Karachi, Pakistan

    M Ishaq & S Z Rasheed

  10. Red Crescent Institute of Cardiology, Hyderabad, Karachi, Pakistan

    F-ur-R Memon

  11. Tabba Heart Institute, Karachi, Pakistan

    B Hanif & M S Lakhani

  12. Department of Cardiology, Liaquat National Hospital, Karachi, Pakistan

    F Ahmed

  13. Department of Microbiology, University of Karachi, Karachi, Pakistan

    S U Kazmi

  14. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

    P Deloukas

  15. Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia

    P Deloukas

  16. Nazarbayev University, Astana, Kazakhstan

    P Frossard

  17. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    P W Franks

  18. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    D Saleheen

Authors
  1. S Ahmad
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  2. W Zhao
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  3. F Renström
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  4. A Rasheed
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  11. M Ishaq
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  14. B Hanif
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  16. F Ahmed
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  21. D Saleheen
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Corresponding authors

Correspondence to P W Franks or D Saleheen.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Ahmad, S., Zhao, W., Renström, F. et al. A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults. Int J Obes 40, 186–190 (2016). https://doi.org/10.1038/ijo.2015.152

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  • DOI: https://doi.org/10.1038/ijo.2015.152

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