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

Shungin, Dmitry, Lund University, Umeå University, Broad Institute, Harvard University, Massachusetts Institute of Technology

Deng, Wei Q., University of Toronto

Varga, Tibor V., Lund University, University of Copenhagen

Luan, Jian'an, University of Cambridge

Mihailov, Evelin, University of Tartu

Metspalu, Andres, University of Tartu

Morris, Andrew P., University of Tartu, University of Liverpool, University of Oxford

Forouhi, Nita G., University of Cambridge

Lindgren, Cecilia, Broad Institute, Harvard University, Massachusetts Institute of Technology, University of Oxford

Magnusson, Patrik K. E., Karolinska Institute

Pedersen, Nancy L., Karolinska Institute

Hallmans, Göran, Umeå University

Chu, Audrey Y., Harvard Medical School

Justice, Anne E., University of North Carolina

Graff, Mariaelisa, University of North Carolina

Winkler, Thomas W., University of Regensburg

Rose, Lynda M., Brigham and Women's Hospital

Langenberg, Claudia, University of Cambridge

Cupples, L. Adrienne, Boston University

Ridker, Paul M., Harvard Medical School, Brigham and Women's Hospital

Wareham, Nicholas J., University of Cambridge

Ong, Ken K., University of Cambridge

Loos, Ruth J. F., Icahn School of Medicine at Mount Sinai

Chasman, Daniel I., Harvard Medical School, Brigham and Women's Hospital

Ingelsson, Erik, Uppsala University, Stanford University School of Medicine

Kilpeläinen, Tuomas O., University of Copenhagen

Scott, Robert A., University of Cambridge

Mägi, Reedik, University of Tartu, University of Oxford

Paré, Guillaume, McMaster University

Franks, Paul W., Lund University, Umeå University, University of Oxford

Published Jun 07, 2018 on Dryad. https://doi.org/10.5061/dryad.q1m7t

Cite this dataset

Shungin, Dmitry et al. (2018). Data from: Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions [Dataset]. Dryad. https://doi.org/10.5061/dryad.q1m7t

Abstract

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 Pv and Pm were 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 Pv and Pm were 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 Pv distribution (Pbinomial<0.05). SNPs from the top 1% of the Pm distribution for BMI had more significant Pv values (PMann-Whitney=1.46E-5), and the odds ratio of SNPs with nominally significant (<0.05) Pm and Pv was 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 Pv values (Pbinomial=8.63E-9 and 8.52E-7 for 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.

Usage notes

Levenes test P values

The zip file contains 10 plain txt files - each of the 10 files have 2 columns, rsID SNP identifier and P values obtained from Levene's test for trait variance heterogeneity between genotypes. The files cover 5 cardiometabolic traits (body mass index, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, total cholesterol), 2 files for each trait. One contains a pruned subset of SNPs and the other one all SNPs as described in the main text of the publication.

LevenePvalues.zip