Text S1 Short descriptions of the cohorts and a full list of acknowledgements. (DOC) Acknowledgments This manuscript is dedicated in memory of Prof. Leena Peltonen whose firm support and guidance had inspired this project immensely. The data annotation, exchange and deposition in public archives have been facilitated by the SIMBioMS platform (Krestyaninova et al, 2009).’’ A full list of acknowledgments is provided in the Text S1. References 1. Cooney M, Cooney H, Dudina A, Graham I (2010) Assesment of cardiovascular risk. Curr Hypertens Rep 12: 384–393. 2. Teslovich T, Musunuru K, Smith A, Edmondson A, Stylianou I, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707–713. 3. Gaziano J, Manson J (1996) Diet and heart disease. The role of fat, alcohol, and antioxidants. Cardiol Clin 14: 69–83. 4. Bullen C (2008) Impact of tobacco smoking and smoking cessation on cardiovascular risk and disease. Expert Rev Cardiovasc Ther 6: 883–895. 5. Kraus W, Slentz C (2009) Exercise training, lipid regulation, and insulin action: a tangled web of cause and effect. Obesity (Silver Spring) 17 Suppl 3: S21–26. 6. Czerwinski S, Mahaney M, Rainwater D, Vandeberg J, MacCluer J, et al. (2004) Gene by smoking interaction: evidence for effects on low-density lipoprotein size and plasma levels of triglyceride and high-density lipoprotein cholesterol. Hum Biol 76: 863–876. 7. Greenfield J, Samaras K, Jenkins A, Kelly P, Spector T, et al. (2004) Do gene- environment interactions influence fasting plasma lipids? A study of twins. Eur J Clin Invest 34: 590–598. 8. Wang X, Ding X, Su S, Spector T, Mangino M, et al. (2009) Heritability of insulin sensitivity and lipid profile depend on BMI: evidence for gene-obesity interaction. Diabetologia 52: 2578–2584. 9. Sent´ı M, Aubo C, Bosch M (1998) The relationship between smoking and triglyceride-rich lipoproteins is modulated by genetic variation in the glycoprotein IIIa gene. Metabolism 47: 1040–1041. 10. Sent´ı M, Elosua R, Toma´s M, Sala J, Masia´ R, et al. (2001) Physical activity modulates the combined effect of a common variant of the lipoprotein lipase gene and smoking on serum triglyceride levels and high-density lipoprotein cholesterol in men. Hum Genet 109: 385–392. 11. Junyent M, Tucker K, Smith C, Garcia-Rios A, Mattei J, et al. (2009) The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study. J Lipid Res 50: 565–573. 12. Corbex M, Poirier O, Fumeron F, Betoulle D, Evans A, et al. (2000) Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene- environment interaction. Genet Epidemiol 19: 64–80. 13. Brand-Herrmann S, Kuznetsova T, Wiechert A, Stolarz K, Tikhonoff V, et al. (2005) Alcohol intake modulates the genetic association between HDL Genome-Wide Screen for G6E Interactions on Lipids Author Contributions Conceived and designed the experiments: LP CMD YSA SR. Performed the experiments: IS AI LCK. Analyzed the data: IS AI LCK PPL RPSM ET JSR CL MM WI JJH VL PH IML TE ZK NWW MVS APS AJK. Contributed reagents/materials/analysis tools: JSV MP TR AKP PS A˚J NS ACH TP IP AT FK AD FR GWM JBW MK TL NBF GW EJCG AP MSS DW AM MS AGU AJ GN CW BHRW MRT MAK JK KOK DIB NLP UG JFW IR HC PPP TDS JCMW JGE VS BAO OTR HEW CG MRJ NGM AH. Wrote the paper: IS AI MIM CMD YSA SR. cholesterol and the PPARgamma2 Pro12Ala polymorphism. J Lipid Res 46: 913–919. 14. Marques-Vidal P, Bongard V, Ruidavets J, Fauvel J, Hanaire-Broutin H, et al. (2003) Obesity and alcohol modulate the effect of apolipoprotein E polymorphism on lipids and insulin. Obes Res 11: 1200–1206. 15. Arya R, Duggirala R, Jenkinson C, Almasy L, Blangero J, et al. (2004) Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans. Am J Hum Genet 74: 272–282. 16. Inouye M, Kettunen J, Soininen P, Silander K, Ripatti S, et al. (2010) Metabonomic, transcriptomic, and genomic variation of a population cohort. Mol Syst Biol Dec 21: 441. 17. Moran T, Katz L, Plata-Salaman C, Schwartz G (1998) Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol 273: R618–R625. 18. Friedewald W, Levy R, Fredrickson D (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499–502. 19. Soininen P, Kangas A, Wu¨rtz P, Tukiainen T, Tynkkynen T, et al. (2009) High- throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism. Analyst 134: 1781–1785. 20. Okazaki M, Usui S, Ishigami M, Sakai N, Nakamura T, et al. (2005) Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography. Thromb Vasc Biol 25: 578–584. 21. Aulchenko Y, Struchalin M, van Duijn C (2010) ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 16: 134. 22. de Bakker P, Ferreira M, Jia X, Neale B, Raychaudhuri S, et al. (2008) Practical aspects of imputation-driven meta-analysis of genome-wide association studies. Hum Mol Genet 17: R122–128. 23. Devlin B, Roeder K, Wasserman L (2001) Genomic control, a new approach to genetic-based association studies. Theor Popul Biol 600: 155–166. 24. R Development Core Team: R: A language and environment for statistical computing, Access date: 2010 Dec 13, http://R-project.org. 25. Pe’er I, Yelensky R, Altshuler D, Daly M (2008) Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32: 381–385. 26. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Static Soc Ser B 57: 289–300. PLoS Genetics | www.plosgenetics.org 8 October 2011 | Volume 7 | Issue 10 | e1002333