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

Ahmad, Shafqat LU ; Zhao, W; Renström, Frida LU ; Rasheed, A; Zaidi, M; Samuel, M; Shah, N; Mallick, N H; Shungin, Dmitry LU and Zaman, K S, et al. (2016) In International Journal of Obesity 40(1). p.186-190
Abstract
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))... (More)
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. (Less)
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International Journal of Obesity
volume
40
issue
1
pages
186 - 190
publisher
Nature Publishing Group
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  • pmid:26278006
  • wos:000367628700027
  • scopus:84953349589
ISSN
1476-5497
DOI
10.1038/ijo.2015.152
language
English
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yes
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0ec1cb35-260a-427a-a06f-36a9b6fb263c (old id 7840841)
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http://www.ncbi.nlm.nih.gov/pubmed/26278006?dopt=Abstract
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2015-09-06 13:24:19
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2017-03-19 03:01:22
@article{0ec1cb35-260a-427a-a06f-36a9b6fb263c,
  abstract     = {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.},
  author       = {Ahmad, Shafqat and Zhao, W and Renström, Frida and Rasheed, A and Zaidi, M and Samuel, M and Shah, N and Mallick, N H and Shungin, Dmitry and Zaman, K S and Ishaq, M and Rasheed, S Z and Memon, F-U-R and Hanif, B and Lakhani, M S and Ahmed, F and Kazmi, S U and Deloukas, P and Frossard, P and Franks, Paul and Saleheen, D},
  issn         = {1476-5497},
  language     = {eng},
  number       = {1},
  pages        = {186--190},
  publisher    = {Nature Publishing Group},
  series       = {International Journal of Obesity},
  title        = {A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.},
  url          = {http://dx.doi.org/10.1038/ijo.2015.152},
  volume       = {40},
  year         = {2016},
}