Shungin, Dmitry and Deng, Wei Q. and Varga, Tibor V. and Luan, Jian'an and Mihailov, Evelin and Metspalu, Andres and Morris, Andrew P. and Forouhi, Nita G. and Lindgren, Cecilia and Magnusson, Patrik K. E. and Pedersen, Nancy L. and Hallmans, Goran and Chu, Audrey Y. and Justice, Anne E. and Graff, Mariaelisa and Winkler, Thomas W. and Rose, Lynda M. and Langenberg, Claudia and Cupples, L. Adrienne and Ridker, Paul M. and Wareham, Nicholas J. and Ong, Ken K. and Loos, Ruth J. F. and Chasman, Daniel I. and Ingelsson, Erik and Kilpelainen, Tuomas O. and Scott, Robert A. and Magi, Reedik and Pare, Guillaume and Franks, Paul W. (2017) Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. PLOS GENETICS, 13 (6): e1006812. ISSN 1553-7404,
Full text not available from this repository. (Request a copy)Abstract
Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (GxE) 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 (P-v), GxE interaction effects (with smoking and physical activity), and marginal genetic effects (P-m). Correlations between P-v and P-m were stronger for SNPs with established marginal effects (Spearman's rho = 0.401 for triglycerides, and rho = 0.236 for BMI) compared to all SNPs. When P-v and P-m were compared for all pruned SNPs, only BMI was statistically significant (Spearman's rho = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the P-v distribution (P-binomial < 0.05). SNPs from the top 1% of the P-m distribution for BMI had more significant P-v values (Pmann-Whitney = 1.46x10(-5)), and the odds ratio of SNPs with nominally significant (< 0.05) P-m and P-v was 1.33 (95% CI: 1.12, 1.57) for BMI. Moreover, BMI SNPs with nominally significant GxE interaction P-values (Pint < 0.05) were enriched with nominally significant P-v values (P-binomial = 8.63x10(-9) and 8.52x10(-7) for SNP x smoking and SNP x physical activity, respectively). We conclude that some loci with strong marginal effects may be good candidates for GxE, and variance-based prioritization can be used to identify them.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BODY-MASS INDEX; GENOME-WIDE METAANALYSIS; PHENOTYPIC VARIABILITY; VARIANTS; OBESITY; INSIGHTS; SNPS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 26 Feb 2019 10:28 |
| URI: | https://pred.uni-regensburg.de/id/eprint/755 |
Actions (login required)
 |
View Item |
