Lund University is celebrating 350 years.


Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

  • Dmitry Shungin
  • Wei Q. Deng
  • Tibor V. Varga
  • Jian'an Luan
  • Evelin Mihailov
  • Andres Metspalu
  • Andrew P. Morris
  • Nita G. Forouhi
  • Cecilia Lindgren
  • Patrik K. E. Magnusson
  • Nancy L. Pedersen
  • Göran Hallmans
  • Audrey Y Chu
  • Anne E. Justice
  • Mariaelisa Graff
  • Thomas W Winkler
  • Lynda M Rose
  • Claudia Langenberg
  • Adrienne L. Cupples
  • Paul M Ridker
  • Nicholas J Wareham
  • Ken K. Ong
  • Ruth J F Loos
  • Daniel I Chasman
  • Erik Ingelsson
  • Tuomas O Kilpeläinen
  • Robert A. Scott
  • Reedik Mägi
  • Guillaume Paré
  • Paul W. Franks
Publishing year: 2017
Language: English
Publication/Series: PLoS Genetics
Volume: 13
Issue: 6
Document type: Journal article
Publisher: Public Library of Science

Abstract english

Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pvand Pmwere stronger for SNPs with established marginal effects (Spearman’s ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pvand Pmwere compared for all pruned SNPs, only BMI was statistically significant (Spearman’s ρ = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the Pvdistribution (Pbinomial<0.05). SNPs from the top 1% of the Pmdistribution for BMI had more significant Pvvalues (PMann–Whitney= 1.46×10−5), and the odds ratio of SNPs with nominally significant (<0.05) Pmand Pvwas 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant G×E interaction P-values (Pint<0.05) were enriched with nominally significant Pvvalues (Pbinomial= 8.63×10−9and 8.52×10−7for SNP × smoking and SNP × physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for G×E, and variance-based prioritization can be used to identify them.


  • Medical Genetics


  • Genetic and Molecular Epidemiology
  • ISSN: 1553-7390
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