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Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Daokun Sun 1 Melissa Richard 1 Solomon Musani 2 Yun Ju Sung 3 Thomas Winkler 4 Karen Schwander 3 Jin Fang Chai 5 Xiuqing Guo 6 Tuomas Kilpeläinen 7 Dina Vojinovic 8 Hugues Aschard 9, 10 Traci Bartz 11 Lawrence Bielak 12 Michael Brown 13 Kumaraswamy Chitrala 14 Fernando Hartwig 15 Andrea R.V.R. Horimoto 16 Yongmei Liu 17 Alisa Manning 18 Raymond Noordam 19 Albert Smith 12 Sarah Harris 20 Brigitte Kühnel Leo-Pekka Lyytikäinen Ilja Nolte Rainer Rauramaa Peter van der Most Rujia Wang Erin Ware Stefan Weiss Wanqing Wen Lisa Yanek Dan Arking Donna Arnett Ana Barac Eric Boerwinkle Ulrich Broeckel Aravinda Chakravarti Yii-Der Ida Chen L. Adrienne Cupples Martha Davigulus Lisa de las Fuentes Renée de Mutsert Paul de Vries Joseph A.C. Delaney Ana Diez Roux Marcus Dörr Jessica Faul Amanda Fretts Linda Gallo Hans Jörgen Grabe C. Charles Gu Tamara Harris Catharina C.A. Hartman Sami Heikkinen M. Arfan Ikram Carmen Isasi W. Craig Johnson Jost Bruno Jonas Robert Kaplan Pirjo Komulainen Jose Krieger Daniel Levy Jianjun Liu Kurt Lohman Annemarie Luik Lisa Martin Thomas Meitinger Yuri Milaneschi Jeff O’connell Walter Palmas Annette Peters Patricia Peyser Laura Pulkki-Råback Leslie Raffel Alex Reiner Kenneth Rice Jennifer Robinson Frits Rosendaal Carsten Oliver Schmidt Pamela Schreiner Lars Schwettmann James Shikany Xiao-Ou Shu Stephen Sidney Mario Sims Jennifer Smith Nona Sotoodehnia Konstantin Strauch E. Shyong Tai Kent Taylor André Uitterlinden Cornelia van Duijn Melanie Waldenberger Hwee-Lin Wee Wen-Bin Wei Gregory Wilson Deng Xuan Jie Yao Donglin Zeng Wei Zhao Xiaofeng Zhu Alan Zonderman Diane Becker Ian Deary Christian Gieger Timo Lakka Terho Lehtimäki Kari North Albertine Oldehinkel Brenda W.J.H. Penninx Harold Snieder Ya-Xing Wang David Weir Wei Zheng Michele Evans W. James Gauderman Vilmundur Gudnason Bernardo Horta Ching-Ti Liu Dennis Mook-Kanamori Alanna Morrison Alexandre Pereira Bruce Psaty Najaf Amin Ervin Fox Charles Kooperberg Xueling Sim Laura Bierut Jerome Rotter Sharon L.R. Kardia Nora Franceschini Dabeeru Rao Myriam Fornage Andrea Horimoto L Adrienne Cupples Joseph Delaney Ana Roux C Charles Gu Catharina Hartman M Arfan Ikram W Craig Johnson Jeff O'Connell E Shyong Tai Brenda Penninx W James Gauderman Sharon Kardia
Abstract : Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A, PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5, CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.
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Submitted on : Friday, January 14, 2022 - 12:38:37 PM
Last modification on : Saturday, January 15, 2022 - 3:02:26 AM

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Daokun Sun, Melissa Richard, Solomon Musani, Yun Ju Sung, Thomas Winkler, et al.. Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits. Human Genetics and Genomics Advances, 2021, 2 (1), pp.100013. ⟨10.1016/j.xhgg.2020.100013⟩. ⟨pasteur-03526221⟩

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