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@ARTICLE{Bentley:279380,
      author       = {Bentley, Amy R and Brown, Michael R and Musani, Solomon K
                      and Schwander, Karen L and Winkler, Thomas W and Sims, Mario
                      and Kilpeläinen, 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 Lyytikäinen,
                      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-Järvinen, 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, André 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 Willems van Dijk, Ko 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
                      Jörgen and Lakka, Timo A and Lehtimäki, 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 Wjh 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},
      collaboration = {Study, Lifelines Cohort},
      othercontributors = {Aguirre-Gamboa, Raul and Deelen, Patrick and Franke, Lude
                          and Kuivenhoven, Jan A and Lopera Maya, Esteban A 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},
      title        = {{M}ulti-ancestry genome-wide association analyses
                      incorporating {SNP}-by-psychosocial interactions identify
                      novel loci for serum lipids.},
      journal      = {Translational Psychiatry},
      volume       = {15},
      number       = {1},
      issn         = {2158-3188},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2025-00757},
      pages        = {207},
      year         = {2025},
      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 (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 < 10-5) were evaluated in up to 55,744
                      independent samples in Stage 2. Significant findings (P < 5
                      × 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.},
      keywords     = {Humans / Genome-Wide Association Study / Polymorphism,
                      Single Nucleotide / Male / Lipids: blood / Lipids: genetics
                      / Female / Gene-Environment Interaction / Adult / Genetic
                      Loci / Middle Aged / Social Support / Lipids (NLM
                      Chemicals)},
      cin          = {AG Grabe},
      ddc          = {610},
      cid          = {I:(DE-2719)5000001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40537477},
      pmc          = {pmc:PMC12179276},
      doi          = {10.1038/s41398-025-03418-z},
      url          = {https://pub.dzne.de/record/279380},
}