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 = 1.46×10-5), 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 = 8.63×10-9 and 8.52×10-7 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.
journal_name
PLoS Genetjournal_title
PLoS geneticsauthors
Shungin D,Deng WQ,Varga TV,Luan J,Mihailov E,Metspalu A,GIANT Consortium.,Morris AP,Forouhi NG,Lindgren C,Magnusson PKE,Pedersen NL,Hallmans G,Chu AY,Justice AE,Graff M,Winkler TW,Rose LM,Langenberg C,Cupples LA,Rdoi
10.1371/journal.pgen.1006812subject
Has Abstractpub_date
2017-06-14 00:00:00pages
e1006812issue
6eissn
1553-7390issn
1553-7404pii
PGENETICS-D-16-00716journal_volume
13pub_type
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