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

  • Shafqat Ahmad
  • W Zhao
  • Frida Renström
  • A Rasheed
  • M Zaidi
  • M Samuel
  • N Shah
  • N H Mallick
  • Dmitry Shungin
  • K S Zaman
  • M Ishaq
  • S Z Rasheed
  • F-U-R Memon
  • B Hanif
  • M S Lakhani
  • F Ahmed
  • S U Kazmi
  • P Deloukas
  • P Frossard
  • Paul Franks
  • D Saleheen
Publishing year: 2016
Language: English
Pages: 186-190
Publication/Series: International Journal of Obesity
Volume: 40
Issue: 1
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

BackgroundObesity 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.MethodsIn the PROMIS study, a cross-sectional study based in Pakistan, we calculated 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, age(2), sex and genetic ancestry.ResultsThe GWHVA analyses yielded a genome-wide significance (P-value=3.1 × 10(-8)) association of the rs140133294 variant at FLJ33534 with BMI variance. 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. No interactions with physical activity were observed. 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.ConclusionIn summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.International Journal of Obesity accepted article preview online, 17 August 2015. doi:10.1038/ijo.2015.152.


  • Public Health, Global Health, Social Medicine and Epidemiology


  • Genetic and Molecular Epidemiology
  • ISSN: 1476-5497
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49



Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00