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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. / Shungin, Dmitry; Deng, Wei Q; Varga, Tibor V; Luan, Jian'an; Mihailov, Evelin; Metspalu, Andres; Morris, Andrew P; Forouhi, Nita G; Lindgren, Cecilia; Magnusson, Patrik K E; Pedersen, Nancy L; Hallmans, Göran; Chu, Audrey Y; Justice, Anne E; Graff, Mariaelisa; Winkler, Thomas W; Rose, Lynda M; Langenberg, Claudia; Cupples, L Adrienne; Ridker, Paul M; Wareham, Nicholas J; Ong, Ken K; Loos, Ruth J F; Chasman, Daniel I; Ingelsson, Erik; Kilpeläinen, Tuomas O; Scott, Robert A; Mägi, Reedik; Paré, Guillaume; Franks, Paul W; GIANT Consortium.

In: P L o S Genetics, Vol. 13, No. 6, e1006812, 06.2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Shungin, D, Deng, WQ, Varga, TV, Luan, J, Mihailov, E, Metspalu, A, 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, Ridker, PM, Wareham, NJ, Ong, KK, Loos, RJF, Chasman, DI, Ingelsson, E, Kilpeläinen, TO, Scott, RA, Mägi, R, Paré, G, Franks, PW & GIANT Consortium 2017, 'Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions', P L o S Genetics, vol. 13, no. 6, e1006812. https://doi.org/10.1371/journal.pgen.1006812

APA

Shungin, D., Deng, W. Q., Varga, T. V., Luan, J., Mihailov, E., Metspalu, A., Morris, A. P., Forouhi, N. G., Lindgren, C., Magnusson, P. K. E., Pedersen, N. L., Hallmans, G., Chu, A. Y., Justice, A. E., Graff, M., Winkler, T. W., Rose, L. M., Langenberg, C., Cupples, L. A., ... GIANT Consortium (2017). Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. P L o S Genetics, 13(6), [e1006812]. https://doi.org/10.1371/journal.pgen.1006812

Vancouver

Shungin D, Deng WQ, Varga TV, Luan J, Mihailov E, Metspalu A et al. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. P L o S Genetics. 2017 Jun;13(6). e1006812. https://doi.org/10.1371/journal.pgen.1006812

Author

Shungin, Dmitry ; Deng, Wei Q ; Varga, Tibor V ; Luan, Jian'an ; Mihailov, Evelin ; Metspalu, Andres ; Morris, Andrew P ; Forouhi, Nita G ; Lindgren, Cecilia ; Magnusson, Patrik K E ; Pedersen, Nancy L ; Hallmans, Göran ; Chu, Audrey Y ; Justice, Anne E ; Graff, Mariaelisa ; Winkler, Thomas W ; Rose, Lynda M ; Langenberg, Claudia ; Cupples, L Adrienne ; Ridker, Paul M ; Wareham, Nicholas J ; Ong, Ken K ; Loos, Ruth J F ; Chasman, Daniel I ; Ingelsson, Erik ; Kilpeläinen, Tuomas O ; Scott, Robert A ; Mägi, Reedik ; Paré, Guillaume ; Franks, Paul W ; GIANT Consortium. / Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. In: P L o S Genetics. 2017 ; Vol. 13, No. 6.

Bibtex

@article{4915c7d6784549289340677886c9be1c,
title = "Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions",
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.",
keywords = "Body Mass Index, Cholesterol, HDL, Cholesterol, LDL, European Continental Ancestry Group, Female, Gene-Environment Interaction, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, Smoking, Journal Article, Meta-Analysis",
author = "Dmitry Shungin and Deng, {Wei Q} and Varga, {Tibor V} and Jian'an Luan and Evelin Mihailov and Andres Metspalu and Morris, {Andrew P} and Forouhi, {Nita G} and Cecilia Lindgren and Magnusson, {Patrik K E} and Pedersen, {Nancy L} and G{\"o}ran Hallmans and Chu, {Audrey Y} and Justice, {Anne E} and Mariaelisa Graff and Winkler, {Thomas W} and Rose, {Lynda M} and Claudia Langenberg 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 Erik Ingelsson and Kilpel{\"a}inen, {Tuomas O} and Scott, {Robert A} and Reedik M{\"a}gi and Guillaume Par{\'e} and Franks, {Paul W} and {GIANT Consortium}",
year = "2017",
month = jun,
doi = "10.1371/journal.pgen.1006812",
language = "English",
volume = "13",
journal = "P L o S Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "6",

}

RIS

TY - JOUR

T1 - Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

AU - Shungin, Dmitry

AU - Deng, Wei Q

AU - Varga, Tibor V

AU - Luan, Jian'an

AU - Mihailov, Evelin

AU - Metspalu, Andres

AU - Morris, Andrew P

AU - Forouhi, Nita G

AU - Lindgren, Cecilia

AU - Magnusson, Patrik K E

AU - Pedersen, Nancy L

AU - Hallmans, Göran

AU - Chu, Audrey Y

AU - Justice, Anne E

AU - Graff, Mariaelisa

AU - Winkler, Thomas W

AU - Rose, Lynda M

AU - Langenberg, Claudia

AU - Cupples, L Adrienne

AU - Ridker, Paul M

AU - Wareham, Nicholas J

AU - Ong, Ken K

AU - Loos, Ruth J F

AU - Chasman, Daniel I

AU - Ingelsson, Erik

AU - Kilpeläinen, Tuomas O

AU - Scott, Robert A

AU - Mägi, Reedik

AU - Paré, Guillaume

AU - Franks, Paul W

AU - GIANT Consortium

PY - 2017/6

Y1 - 2017/6

N2 - 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.

AB - 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.

KW - Body Mass Index

KW - Cholesterol, HDL

KW - Cholesterol, LDL

KW - European Continental Ancestry Group

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Heterogeneity

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Male

KW - Obesity

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Risk Factors

KW - Smoking

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1371/journal.pgen.1006812

DO - 10.1371/journal.pgen.1006812

M3 - Journal article

C2 - 28614350

VL - 13

JO - P L o S Genetics

JF - P L o S Genetics

SN - 1553-7390

IS - 6

M1 - e1006812

ER -

ID: 182933575