A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.
(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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https://lup.lub.lu.se/record/7840841
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- publishing date
- 2016
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- Contribution to journal
- publication status
- published
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- in
- International Journal of Obesity
- volume
- 40
- issue
- 1
- pages
- 186 - 190
- publisher
- Nature Publishing Group
- external identifiers
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- pmid:26278006
- wos:000367628700027
- scopus:84953349589
- pmid:26278006
- ISSN
- 1476-5497
- DOI
- 10.1038/ijo.2015.152
- language
- English
- LU publication?
- 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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- 2016-04-01 09:52:32
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- 2022-04-11 23:45:14
@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}},
doi = {{10.1038/ijo.2015.152}},
volume = {{40}},
year = {{2016}},
}