Meta-Analysis of Joint Test of SNP and SNP-Environment Interaction with Heterogeneity

Jin Q.a,b· Shi G.a

Author affiliations

aState Key Laboratory of Integrated Services Networks, Xidian University, Xi’an, China
bApplied Science College, Taiyuan University of Science and Technology, Taiyuan, China

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Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: September 05, 2020
Accepted: July 29, 2021
Published online: October 26, 2021

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://www.karger.com/HHE

Abstract

Many complex diseases are caused by single nucleotide polymorphisms (SNPs), environmental factors, and the interaction between SNPs and environment. Joint tests of the SNP and SNP-environment interaction effects (JMA) and meta-regression (MR) are commonly used to evaluate these SNP-environment interactions. However, these two methods do not consider genetic heterogeneity. We previously presented a random-effect MR, which provided higher power than the MR in datasets with high heterogeneity. However, this method requires group-level data, which sometimes are not available. Given this, we designed this study to evaluate the introduction of the random effects of SNP and SNP-environment interaction into the JMA, and then extended this to the random effect model. Likelihood ratio statistic is applied to test the JMA and the new method we proposed in this paper. We evaluated the null distributions of these tests, and the powers for this method. This method was verified by simulation and was shown to provide similar powers to the random effect meta-regression method (RMR). However, this method only requires study-level data which relaxed the condition of the RMR. Our study suggests that this method is more suitable for finding the association between SNP and diseases in the absence of group-level data.

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References Hardy J, Singleton A. Genomewide association studies and human disease. N Engl J Med. 2009 Apr;360(17):1759–68. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007 Jun;316(5829):1341–5. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’er I, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature. 2009 Aug;460(7256):753–7. Lewis SN, Nsoesie E, Weeks C, Qiao D, Zhang L. Prediction of disease and phenotype associations from genome-wide association studies. PLoS One. 2011;6(11):e27175. Palmer ND, McDonough CW, Hicks PJ, Roh BH, Wing MR, An SS, et al.; DIAGRAM Consortium; MAGIC Investigators. A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One. 2012;7(1):e29202. Petitti DB. Statistical Methods in Meta-Analysis. New York: Oxford Univ. Press; 2000. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature. 2009 Oct;461(7265):747–53. Xu X, Shi G, Nehorai A. Meta-regression of gene-environment interaction in genome-wide association studies. IEEE Trans Nanobioscience. 2013 Dec;12(4):354–62. Thomas D. Gene—environment-wide association studies: emerging approaches. Nat Rev Genet. 2010 Apr;11(4):259–72. Gauderman WJ, Mukherjee B, Aschard H, Hsu L, Lewinger JP, Patel CJ, et al. Update on the state of the science for analytical methods for gene-environment interactions. Am J Epidemiol. 2017 Oct;186(7):762–70. Kim J, Ziyatdinov A, Laville V, Hu FB, Rimm E, Kraft P, et al. Joint Analysis of Multiple Interaction Parameters in Genetic Association Studies. Genetics. 2019 Feb;211(2):483–94. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, Chasman DI, et al.; CHARGE-HF consortium. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011 Sep;478(7367):103–9. Wain LV, Verwoert GC, O’Reilly PF, Shi G, Johnson T, Johnson AD, et al.; LifeLines Cohort Study; EchoGen consortium; AortaGen Consortium; CHARGE Consortium Heart Failure Working Group; KidneyGen consortium; CKDGen consortium; Cardiogenics consortium; CardioGram. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nat Genet. 2011 Sep;43(10):1005–11. Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, et al. Genome-wide association study of blood pressure and hypertension. Nat Genet. 2009 Jun;41(6):677–87. Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, et al.; Wellcome Trust Case Control Consortium. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet. 2009 Jun;41(6):666–76. Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet. 2011 Jun;43(6):531–8. Ehret GB, Caulfield MJ. Genes for blood pressure: an opportunity to understand hypertension. Eur Heart J. 2013 Apr;34(13):951–61. Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997 May;277(20):1624–32. He J, Kelly TN, Zhao Q, Li H, Huang J, Wang L, et al. Genome-wide association study identifies 8 novel loci associated with blood pressure responses to interventions in Han Chinese. Circ Cardiovasc Genet. 2013 Dec;6(6):598–607. Li C, He J, Chen J, Zhao J, Gu D, Hixson JE, et al. Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Circ Cardiovasc Genet. 2017 Dec;10(6):e001811. Ritz BR, Chatterjee N, Garcia-Closas M, Gauderman WJ, Pierce BL, Kraft P, et al. Lessons Learned From Past Gene-Environment Interaction Successes. Am J Epidemiol. 2017 Oct;186(7):778–86. Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat Rev Genet. 2009 Apr;10(4):241–51. de Bakker PI, Ferreira MA, Jia X, Neale BM, Raychaudhuri S, Voight BF. Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet. 2008 Oct;17 R2:R122–8. Cantor RM, Lange K, Sinsheimer JS. Prioritizing GWAS results: A review of statistical methods and recommendations for their application. Am J Hum Genet. 2010 Jan;86(1):6–22. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al.; Type 1 Diabetes Genetics Consortium. Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet. 2009 Jun;41(6):703–7. Escaramís G, Docampo E, Rabionet R. A decade of structural variants: description, history and methods to detect structural variation. Brief Funct Genomics. 2015 Sep;14(5):305–14. Manning AK, LaValley M, Liu CT, Rice K, An P, Liu Y, et al. Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP × environment regression coefficients. Genet Epidemiol. 2011 Jan;35(1):11–8. Shi G, Nehorai A. Robustness of meta-analyses in finding gene × environment interactions. PLoS One. 2017 Mar;12(3):e0171446. Evangelou E, Ioannidis JP. Meta-analysis methods for genome-wide association studies and beyond. Nat Rev Genet. 2013 Jun;14(6):379–89. Manchia M, Cullis J, Turecki G, Rouleau GA, Uher R, Alda M. The impact of phenotypic and genetic heterogeneity on results of genome wide association studies of complex diseases. PLoS One. 2013 Oct;8(10):e76295. Martin AR, Gignoux CR, Walters RK, Wojcik GL, Neale BM, Gravel S, et al. Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations. Am J Hum Genet. 2017 Apr;100(4):635–49. Sarhangi N, Sharifi F, Hashemian L, Hassani Doabsari M, Heshmatzad K, Rahbaran M, et al. PPARG (Pro12Ala) genetic variant and risk of T2DM: a systematic review and meta-analysis. Sci Rep. 2020 Jul;10(1):12764. Li C, Wu D, Lu Q. Set-based genetic association and interaction tests for survival outcomes based on weighted V statistics. Genet Epidemiol. 2021 Feb;45(1):46–63. Reiter JG, Baretti M, Gerold JM, Makohon-Moore AP, Daud A, Iacobuzio-Donahue CA, et al. An analysis of genetic heterogeneity in untreated cancers. Nat Rev Cancer. 2019 Nov;19(11):639–50. Han B, Eskin E. Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies. Am J Hum Genet. 2011 May;88(5):586–98. Jin Q, Shi G. Meta-analysis of SNP-environment interaction with heterogeneity. Hum Hered. 2019;84(3):117–26. Self SG, Liang KY. Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions. J Am Stat Assoc. 1987;82(398):605–10. Stram DO, Lee JW. Variance components testing in the longitudinal mixed effects model. Biometrics. 1994 Dec;50(4):1171–7. Dunson DB, editor. Random Effect and Latent Variable Model Selection. Berlin: Springer; 2008. Stoel RD, Garre FG, Dolan C, van den Wittenboer G. On the likelihood ratio test in structural equation modeling when parameters are subject to boundary constraints. Psychol Methods. 2006 Dec;11(4):439–55. Lee CH, Eskin E, Han B. Increasing the power of meta-analysis of genome-wide association studies to detect heterogeneous effects. Bioinformatics. 2017 Jul;33(14):i379–88. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: September 05, 2020
Accepted: July 29, 2021
Published online: October 26, 2021

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0

ISSN: 0001-5652 (Print)
eISSN: 1423-0062 (Online)

For additional information: https://www.karger.com/HHE

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