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

Publication

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

Journal Paper/Review - Aug 17, 2015

Ahmad S, Memon F-Ur-R, Hanif B, Lakhani M S, Ahmed F, Kazmi S U, Deloukas P, Frossard P, Franks P W, Rasheed S Z, Ishaq M, Zaman K S, Zhao W, Renström Frida, Rasheed A, Zaidi M, Samuel M, Shah N, Mallick N H, Shungin D, Saleheen D

Citation

Ahmad S, Memon F, Hanif B, Lakhani M, Ahmed F, Kazmi S, Deloukas P, Frossard P, Franks P, Rasheed S, Ishaq M, Zaman K, Zhao W, Renström F, Rasheed A, Zaidi M, Samuel M, Shah N, Mallick N, Shungin D, Saleheen D. A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults. Int J Obes (Lond) 2015; 40:186-90.

Type

Journal Paper/Review (English)

Journal

Int J Obes (Lond) 2015; 40

Publication Date

Aug 17, 2015

Issn Electronic

1476-5497

Pages

186-90

Brief description/objective

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, age(2), 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.