Bentley, Amy R. and Brown, Michael R. and Musani, Solomon K. and Schwander, Karen L. and Winkler, Thomas W. and Sims, Mario and Kilpelainen, Tuomas O. and Aschard, Hugues and Bartz, Traci M. and Bielak, Lawrence F. and Chai, Jin-Fang and Chitrala, Kumaraswamy Naidu and Franceschini, Nora and Graff, Mariaelisa and Guo, Xiuqing and Hartwig, Fernando P. and Horimoto, Andrea R. V. R. and Lim, Elise and Liu, Yongmei and Manning, Alisa K. and Nolte, Ilja M. and Noordam, Raymond and Richard, Melissa A. and Smith, Albert V. and Sung, Yun Ju and Vojinovic, Dina and Wang, Rujia and Wang, Yujie and Feitosa, Mary F. and Harris, Sarah E. and Lyytikainen, Leo-Pekka and Pistis, Giorgio and Rauramaa, Rainer and van der Most, Peter J. and Ware, Erin and Weiss, Stefan and Wen, Wanqing and Yanek, Lisa R. and Arking, Dan E. and Arnett, Donna K. and Ballantyne, Christie and Boerwinkle, Eric and Chen, Yii-Der Ida and Daviglus, Martha L. and de las Fuentes, Lisa and de Vries, Paul S. and Delaney, Joseph A. C. and Fretts, Amanda M. and Ekunwe, Lynette and Faul, Jessica D. and Gallo, Linda C. and Heikkinen, Sami and Homuth, Georg and Ikram, M. Arfan and Isasi, Carmen R. and Jonas, Jost Bruno and Keltikangas-Jarvinen, Liisa and Komulainen, Pirjo and Kraja, Aldi T. and Krieger, Jose E. and Launer, Lenore and Liu, Jianjun and Lohman, Kurt and Luik, Annemarie I. and Manichaikul, Ani W. and Marques-Vidal, Pedro and Milaneschi, Yuri and Mwasongwe, Stanford E. and O'Connell, Jeffrey R. and Rice, Kenneth and Rich, Stephen S. and Schreiner, Pamela J. and Schwettmann, Lars and Shikany, James M. and Shu, Xiao-ou and Smith, Jennifer A. and Snieder, Harold and Sotoodehnia, Nona and Tai, E. Shyong and Taylor, Kent D. and Tinker, Lesley and Tsai, Michael Y. and Uitterlinden, Andre G. and van Duijn, Cornelia M. and van Heemst, Diana and Waldenberger, Melanie and Wallace, Robert B. and Wee, Hwee-Lin and Weir, David R. and Wei, Wen-Bin and van Dijk, Ko Willems and Wilson, Gregory and Yao, Jie and Young, Kristin L. and Zhang, Xiaoyu and Zhao, Wei and Zhu, Xiaofeng and Zonderman, Alan B. and Deary, Ian J. and Gieger, Christian and Grabe, Hans Jorgen and Lakka, Timo A. and Lehtimaki, Terho and Oldehinkel, Albertine J. and Preisig, Martin and Wang, Ya-Xing and Zheng, Wei and Evans, Michele K. and Province, Michael and Gauderman, James and Gudnason, Vilmundur and Hartman, Catharina A. and Horta, Bernardo L. and Kardia, Sharon L. R. and Kooperberg, Charles and Liu, Ching-Ti and Mook-Kanamori, Dennis O. and Penninx, Brenda W. J. H. and Pereira, Alexandre C. and Peyser, Patricia A. and Psaty, Bruce M. and Rotter, Jerome I. and Sim, Xueling and North, Kari E. and Rao, Dabeeru C. and Bierut, Laura and Miller, Clint L. and Morrison, Alanna C. and Rotimi, Charles N. and Fornage, Myriam and Fox, Ervin R. and Aguirre-Gamboa, Raul and Deelen, Patrick and Franke, Lude and Kuivenhoven, Jan A. and Maya, Esteban A. Lopera and Nolte, Ilja M. and Sanna, Serena and Snieder, Harold and Swertz, Morris A. and Visscher, Peter M. and Vonk, Judith M. and Wijmenga, Cisca and Wray, Naomi (2025) Multi-ancestry genome-wide association analyses incorporating SNP-by-psychosocial interactions identify novel loci for serum lipids. TRANSLATIONAL PSYCHIATRY, 15 (1): 207. ISSN 2158-3188,
Full text not available from this repository. (Request a copy)Abstract
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 (GxPsy) study in up to 133,157 individuals to evaluate if GxPsy influences serum lipid levels. We conducted a two-stage meta-analysis of GxPsy 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 GxPsy analyses on up to 77,413 individuals and promising associations (P < 10(-5)) were evaluated in up to 55,744 independent samples in Stage 2. Significant findings (P < 5 x 10(-8)) were identified based on meta-analyses of the two stages. There were 10,230 variants from 120 loci significantly associated with serum lipids. We identified novel associations for variants in four loci using the 1df test of interaction, and five additional loci using the 2df joint test that were independent of known lipid loci. Of these 9 loci, 7 could not have been detected without modeling the interaction as there was no evidence of association in a standard GWAS model. The genetic diversity of included samples was key in identifying these novel loci: four of the lead variants displayed very low frequency in European ancestry populations. Functional annotation highlighted promising loci for further experimental follow-up, particularly rs73597733 (MACROD2), rs59808825 (GRAMD1B), and rs11702544 (RRP1B). Notably, one of the genes in identified loci (RRP1B) was found to be a target of the approved drug Atenolol suggesting potential for drug repurposing. Overall, our findings suggest that taking interaction between genetic variants and psychosocial factors into account and including genetically diverse populations can lead to novel discoveries for serum lipids.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-ENVIRONMENT INTERACTION; METAANALYSIS; CHOLESTEROL; SCHIZOPHRENIA; VARIANTS; RISK; INDIVIDUALS; DEPRESSION; DISCOVERY; RELATIVES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2026 10:47 |
| Last Modified: | 23 Mar 2026 10:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68118 |
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