Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions. Shungin, D., Deng, W. Q, Varga, T. V, Luan, J., Mihailov, E., Metspalu, A., GIANT Consortium, 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., Ridker, P. M, Wareham, N. J, Ong, K. K, Loos, R. J F, Chasman, D. I, Ingelsson, E., Kilpeläinen, T. O, Scott, R. A, Mägi, R., Paré, G., & Franks, P. W PLoS Genet, 13(6):e1006812, Jun, 2017. ![Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{Shungin:2017aa,
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.},
author = {Shungin, Dmitry and Deng, Wei Q and Varga, Tibor V and Luan, Jian'an and Mihailov, Evelin and Metspalu, Andres and {GIANT Consortium} and Morris, Andrew P and Forouhi, Nita G and Lindgren, Cecilia and Magnusson, Patrik K E and Pedersen, Nancy L and Hallmans, G{\"o}ran 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 Kilpel{\"a}inen, Tuomas O and Scott, Robert A and M{\"a}gi, Reedik and Par{\'e}, Guillaume and Franks, Paul W},
date-added = {2024-05-19 21:02:34 -0400},
date-modified = {2024-05-19 21:02:34 -0400},
doi = {10.1371/journal.pgen.1006812},
journal = {PLoS Genet},
journal-full = {PLoS genetics},
mesh = {Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; 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; White People},
month = {Jun},
number = {6},
pages = {e1006812},
pmc = {PMC5489225},
pmid = {28614350},
url = {https://pubmed.ncbi.nlm.nih.gov/28614350/},
pst = {epublish},
title = {Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions},
volume = {13},
year = {2017},
bdsk-url-1 = {https://doi.org/10.1371/journal.pgen.1006812}}
Downloads: 0
{"_id":"BCKxc79zu2iSipgs8","bibbaseid":"shungin-deng-varga-luan-mihailov-metspalu-giantconsortium-morris-etal-rankingandcharacterizationofestablishedbmiandlipidassociatedlociascandidatesforgeneenvironmentinteractions-2017","author_short":["Shungin, D.","Deng, W. Q","Varga, T. V","Luan, J.","Mihailov, E.","Metspalu, A.","GIANT Consortium","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.","Ridker, P. M","Wareham, N. J","Ong, K. K","Loos, R. J F","Chasman, D. I","Ingelsson, E.","Kilpeläinen, T. O","Scott, R. A","Mägi, R.","Paré, G.","Franks, P. W"],"bibdata":{"bibtype":"article","type":"article","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.","author":[{"propositions":[],"lastnames":["Shungin"],"firstnames":["Dmitry"],"suffixes":[]},{"propositions":[],"lastnames":["Deng"],"firstnames":["Wei","Q"],"suffixes":[]},{"propositions":[],"lastnames":["Varga"],"firstnames":["Tibor","V"],"suffixes":[]},{"propositions":[],"lastnames":["Luan"],"firstnames":["Jian'an"],"suffixes":[]},{"propositions":[],"lastnames":["Mihailov"],"firstnames":["Evelin"],"suffixes":[]},{"propositions":[],"lastnames":["Metspalu"],"firstnames":["Andres"],"suffixes":[]},{"firstnames":[],"propositions":[],"lastnames":["GIANT Consortium"],"suffixes":[]},{"propositions":[],"lastnames":["Morris"],"firstnames":["Andrew","P"],"suffixes":[]},{"propositions":[],"lastnames":["Forouhi"],"firstnames":["Nita","G"],"suffixes":[]},{"propositions":[],"lastnames":["Lindgren"],"firstnames":["Cecilia"],"suffixes":[]},{"propositions":[],"lastnames":["Magnusson"],"firstnames":["Patrik","K","E"],"suffixes":[]},{"propositions":[],"lastnames":["Pedersen"],"firstnames":["Nancy","L"],"suffixes":[]},{"propositions":[],"lastnames":["Hallmans"],"firstnames":["Göran"],"suffixes":[]},{"propositions":[],"lastnames":["Chu"],"firstnames":["Audrey","Y"],"suffixes":[]},{"propositions":[],"lastnames":["Justice"],"firstnames":["Anne","E"],"suffixes":[]},{"propositions":[],"lastnames":["Graff"],"firstnames":["Mariaelisa"],"suffixes":[]},{"propositions":[],"lastnames":["Winkler"],"firstnames":["Thomas","W"],"suffixes":[]},{"propositions":[],"lastnames":["Rose"],"firstnames":["Lynda","M"],"suffixes":[]},{"propositions":[],"lastnames":["Langenberg"],"firstnames":["Claudia"],"suffixes":[]},{"propositions":[],"lastnames":["Cupples"],"firstnames":["L","Adrienne"],"suffixes":[]},{"propositions":[],"lastnames":["Ridker"],"firstnames":["Paul","M"],"suffixes":[]},{"propositions":[],"lastnames":["Wareham"],"firstnames":["Nicholas","J"],"suffixes":[]},{"propositions":[],"lastnames":["Ong"],"firstnames":["Ken","K"],"suffixes":[]},{"propositions":[],"lastnames":["Loos"],"firstnames":["Ruth","J","F"],"suffixes":[]},{"propositions":[],"lastnames":["Chasman"],"firstnames":["Daniel","I"],"suffixes":[]},{"propositions":[],"lastnames":["Ingelsson"],"firstnames":["Erik"],"suffixes":[]},{"propositions":[],"lastnames":["Kilpeläinen"],"firstnames":["Tuomas","O"],"suffixes":[]},{"propositions":[],"lastnames":["Scott"],"firstnames":["Robert","A"],"suffixes":[]},{"propositions":[],"lastnames":["Mägi"],"firstnames":["Reedik"],"suffixes":[]},{"propositions":[],"lastnames":["Paré"],"firstnames":["Guillaume"],"suffixes":[]},{"propositions":[],"lastnames":["Franks"],"firstnames":["Paul","W"],"suffixes":[]}],"date-added":"2024-05-19 21:02:34 -0400","date-modified":"2024-05-19 21:02:34 -0400","doi":"10.1371/journal.pgen.1006812","journal":"PLoS Genet","journal-full":"PLoS genetics","mesh":"Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; 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; White People","month":"Jun","number":"6","pages":"e1006812","pmc":"PMC5489225","pmid":"28614350","url":"https://pubmed.ncbi.nlm.nih.gov/28614350/","pst":"epublish","title":"Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions","volume":"13","year":"2017","bdsk-url-1":"https://doi.org/10.1371/journal.pgen.1006812","bibtex":"@article{Shungin:2017aa,\n\tabstract = {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.},\n\tauthor = {Shungin, Dmitry and Deng, Wei Q and Varga, Tibor V and Luan, Jian'an and Mihailov, Evelin and Metspalu, Andres and {GIANT Consortium} and Morris, Andrew P and Forouhi, Nita G and Lindgren, Cecilia and Magnusson, Patrik K E and Pedersen, Nancy L and Hallmans, G{\\\"o}ran 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 Kilpel{\\\"a}inen, Tuomas O and Scott, Robert A and M{\\\"a}gi, Reedik and Par{\\'e}, Guillaume and Franks, Paul W},\n\tdate-added = {2024-05-19 21:02:34 -0400},\n\tdate-modified = {2024-05-19 21:02:34 -0400},\n\tdoi = {10.1371/journal.pgen.1006812},\n\tjournal = {PLoS Genet},\n\tjournal-full = {PLoS genetics},\n\tmesh = {Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; 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; White People},\n\tmonth = {Jun},\n\tnumber = {6},\n\tpages = {e1006812},\n\tpmc = {PMC5489225},\n\tpmid = {28614350},\n\turl = {https://pubmed.ncbi.nlm.nih.gov/28614350/},\n\tpst = {epublish},\n\ttitle = {Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions},\n\tvolume = {13},\n\tyear = {2017},\n\tbdsk-url-1 = {https://doi.org/10.1371/journal.pgen.1006812}}\n\n","author_short":["Shungin, D.","Deng, W. Q","Varga, T. V","Luan, J.","Mihailov, E.","Metspalu, A.","GIANT Consortium","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.","Ridker, P. M","Wareham, N. J","Ong, K. K","Loos, R. J F","Chasman, D. I","Ingelsson, E.","Kilpeläinen, T. O","Scott, R. A","Mägi, R.","Paré, G.","Franks, P. W"],"key":"Shungin:2017aa","id":"Shungin:2017aa","bibbaseid":"shungin-deng-varga-luan-mihailov-metspalu-giantconsortium-morris-etal-rankingandcharacterizationofestablishedbmiandlipidassociatedlociascandidatesforgeneenvironmentinteractions-2017","role":"author","urls":{"Paper":"https://pubmed.ncbi.nlm.nih.gov/28614350/"},"metadata":{"authorlinks":{}},"downloads":0,"html":""},"bibtype":"article","biburl":"https://bibbase.org/network/files/gqwqyBJuHtD7EvhhG","dataSources":["Y9DJHroPCz3Lqc5T2"],"keywords":[],"search_terms":["ranking","characterization","established","bmi","lipid","associated","loci","candidates","gene","environment","interactions","shungin","deng","varga","luan","mihailov","metspalu","giant consortium","morris","forouhi","lindgren","magnusson","pedersen","hallmans","chu","justice","graff","winkler","rose","langenberg","cupples","ridker","wareham","ong","loos","chasman","ingelsson","kilpeläinen","scott","mägi","paré","franks"],"title":"Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions","year":2017}