Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids.
Bentley AR., Brown MR., Musani SK., Schwander KL., Winkler TW., Sims M., Kilpeläinen TO., Aschard H., Bartz TM., Bielak LF., Chai J-F., Chitrala KN., Franceschini N., Graff M., Guo X., Hartwig FP., Horimoto ARVR., Lim E., Liu Y., Manning AK., Nolte IM., Noordam R., Richard MA., Smith AV., Sung YJ., Vojinovic D., Wang R., Wang Y., Feitosa MF., Harris SE., Lyytikäinen L-P., Pistis G., Rauramaa R., van der Most PJ., Ware E., Weiss S., Wen W., Yanek LR., Arking DE., Arnett DK., Ballantyne C., Boerwinkle E., Chen Y-DI., Daviglus ML., de Las Fuentes L., de Vries PS., Delaney JAC., Fretts AM., Ekunwe L., Faul JD., Gallo LC., Heikkinen S., Homuth G., Ikram MA., Isasi CR., Jonas JB., Keltikangas-Järvinen L., Komulainen P., Kraja AT., Krieger JE., Launer L., Lifelines Cohort Study None., Liu J., Lohman K., Luik AI., Manichaikul AW., Marques-Vidal P., Milaneschi Y., Mwasongwe SE., O'Connell JR., Rice K., Rich SS., Schreiner PJ., Schwettmann L., Shikany JM., Shu X-O., Smith JA., Snieder H., Sotoodehnia N., Tai ES., Taylor KD., Tinker L., Tsai MY., Uitterlinden AG., van Duijn CM., van Heemst D., Waldenberger M., Wallace RB., Wee H-L., Weir DR., Wei W-B., Willems van Dijk K., Wilson G., Yao J., Young KL., Zhang X., Zhao W., Zhu X., Zonderman AB., Deary IJ., Gieger C., Grabe HJ., Lakka TA., Lehtimäki T., Oldehinkel AJ., Preisig M., Wang Y-X., Zheng W., Evans MK., Province M., Gauderman J., Gudnason V., Hartman CA., Horta BL., Kardia SLR., Kooperberg C., Liu C-T., Mook-Kanamori DO., Penninx BW., Pereira AC., Peyser PA., Psaty BM., Rotter JI., Sim X., North KE., Rao DC., Bierut L., Miller CL., Morrison AC., Rotimi CN., Fornage M., Fox ER.
Serum lipid levels, which are influenced by both genetic and environmental factors, are key determinants of cardiometabolic health and are influenced by both genetic and environmental factors. Improving our understanding of their underlying biological mechanisms can have important public health and therapeutic implications. Although psychosocial factors, including depression, anxiety, and perceived social support, are associated with serum lipid levels, it is unknown if they modify the effect of genetic loci that influence lipids. We conducted a genome-wide gene-by-psychosocial factor interaction (G×Psy) study in up to 133,157 individuals to evaluate if G×Psy influences serum lipid levels. We conducted a two-stage meta-analysis of G×Psy using both a one-degree of freedom (1df) interaction test and a joint 2df test of the main and interaction effects. In Stage 1, we performed G×Psy analyses on up to 77,413 individuals and promising associations (P