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

Ahmad, Shafqat; Zhao, Wei; Renström, Frida; Rasheed, Awais; Zaidi, Mozzam; Samuel, Maria; Shah, Nabi; Mallick, Nadeem Hayat; Shungin, Dmitry; Zaman, Khan Shah; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, F-U-R; Hanif, Bashir; Lakhani, Muhammad Shakir; Ahmed, Faisal; Kazmi, Shahana Urooj; Deloukas, Panos; Frossard, Philippe; Franks, Paul W.; Saleheen, Danish

doi:10.1038/ijo.2015.152

Cited by 18 publications

(26 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there was no evidence of association between variation at rs1051730 and BMI in never smokers, each additional risk allele (T) was associated with a BMI decrease of 0.16 and 0.33 kg/m 2 among former and current smokers respectively [165]. A separate study of 14131 Pakistani adults reported another gene × smoking interaction: the minor allele (T) in FLJ33534 was associated with lower BMI in current smokers and positively associated with BMI among adults who had never smoked [166]. A number of gene × smoking interactions were identified when African Americans and Caucasians were analysed separately, but no significant interactions were observed in the overall sample from the Southern Community Cohort Study [167].…”

Section: Obesity-predisposing Gene Variants Interact With Smoking Statusmentioning

confidence: 96%

The importance of gene–environment interactions in human obesity

2016

View full text Add to dashboard Cite

The worldwide obesity epidemic has been mainly attributed to lifestyle changes. However, who becomes obese in an obesity-prone environment is largely determined by genetic factors. In the last 20 years, important progress has been made in the elucidation of the genetic architecture of obesity. In parallel with successful gene identifications, the number of gene-environment interaction (GEI) studies has grown rapidly. This paper reviews the growing body of evidence supporting gene-environment interactions in the field of obesity. Heritability, monogenic and polygenic obesity studies provide converging evidence that obesity-predisposing genes interact with a variety of environmental, lifestyle and treatment exposures. However, some skepticism remains regarding the validity of these studies based on several issues, which include statistical modelling, confounding, low replication rate, underpowered analyses, biological assumptions and measurement precision. What follows in this review includes (1) an introduction to the study of GEI, (2) the evidence of GEI in the field of obesity, (3) an outline of the biological mechanisms that may explain these interaction effects, (4) methodological challenges associated with GEI studies and potential solutions, and (5) future directions of GEI research. Thus far, this growing body of evidence has provided a deeper understanding of GEI influencing obesity and may have tremendous applications in the emerging field of personalized medicine and individualized lifestyle recommendations.

show abstract

Section: Obesity-predisposing Gene Variants Interact With Smoking Statusmentioning

confidence: 96%

The importance of gene–environment interactions in human obesity

2016

View full text Add to dashboard Cite

show abstract

“…Among Asian Indians, Been et al confirmed the association of MC4R (rs12970134) with BMI (134). Genome-wide heterogeneity of variance analysis in 14,131 Pakistani individuals identified an interaction with smoking status and a novel obesity variant in FLJ33534 (rs140133294) on BMI (135). Meta-analysis of 9,881 African-Americans has demonstrated an association between FTO (rs3751812 and rs9941349) and obesity, while two smaller GWAS with individuals of African ancestry provide some evidence of replication of the association between MC4R (rs6567160 and rs17782313) and BMI (136,137).…”

Section: Gwas For Obesity In European and Non-european Populationsmentioning

confidence: 97%

“…When genetic variants in these genes were analysed with regards to environment, a stronger association between FTO , weight and living in an urban environment was found in comparison with those living in a rural environment . A novel interaction between smoking status and the FLJ33534 locus on BMI has recently been reported in a Pakistani population . G × G and G × E interaction remain largely unexplored due to statistical challenges associated with inadequate sample sizes but may explain some of the missing heritability .…”

Section: Polygenic Forms Of Obesity and Ethnic Diversitymentioning

confidence: 99%

Ethnic and population differences in the genetic predisposition to human obesity

2017

View full text Add to dashboard Cite

SummaryObesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments.

show abstract

“…Increased statistical power needed to identify SNPs associated with obesity traits under a recessive mode of inheritance is expected because of the high level of homozygosity in Pakistanis . GWAS for obesity traits have already been reported in South Asian populations . However, conducting a large‐scale genome‐wide association meta‐analysis in more than 100,000 participants of South Asian ancestry is critical to uncover the genetic basis of polygenic obesity in this population, as previously reported in European and East Asian studies .…”

Section: Genetic Elucidation Of Obesity In Pakistani Populationmentioning

confidence: 94%

“…FTO rs9939609 was more strongly associated with weight and BMI in siblings living in urban than rural area of India, an observation made in an independent study in South Asians . In the cross‐sectional PROMIS study, a genome‐wide heterogeneity of variance analysis for BMI was conducted in 14,131 participants . The intronic variant, rs140133294, in the FLJ33544 gene was associated with BMI variance.…”

Section: Genetic Elucidation Of Obesity In Pakistani Populationmentioning

confidence: 96%

Obesity genetics: insights from the Pakistani population

et al. 2017

View full text Add to dashboard Cite

The Pakistani population is extensively diverse, indicating a genetic admixture of European and Central/West Asian migrants with indigenous South Asian gene pools. Pakistanis are organized in different ethnicities/castes based on cultural, linguistic and geographical origin. While Pakistan is facing a rapid nutritional transition, the rising prevalence of obesity is driving a growing burden of health complications and mortality. This represents a unique opportunity for the research community to study the interplay between obesogenic environmental changes and obesity predisposing genes in the time frame of one generation. This review recapitulates the ancestral origins of Pakistani population, the societal determinants of the rise in obesity and its governmental management. We describe the contribution of syndromic, monogenic non-syndromic and polygenic obesity genes identified in the Pakistani population. We then discuss the utility of gene identification approaches based on large consanguineous families and original gene × environment interaction study designs in discovering new obesity genes and causal pathways. Elucidation of the genetic basis of obesity in the Pakistani population may result in improved methods of obesity prevention and treatment globally.

show abstract

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

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

Cited by 18 publications

References 28 publications

The importance of gene–environment interactions in human obesity

The importance of gene–environment interactions in human obesity

Ethnic and population differences in the genetic predisposition to human obesity

Obesity genetics: insights from the Pakistani population

Contact Info

Product

Resources

About