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

1 University of Texas Health Science Center
2 UMMC - University of Mississippi Medical Center
3 Washington University School of Medicine in St. Louis
4 University of Regensburg
5 NUS - National University of Singapore
6 Harbor UCLA Medical Center [Torrance, Ca.]
7 ITU - IT University of Copenhagen
8 Erasmus MC - Erasmus University Medical Center [Rotterdam]
9 Harvard School of Public Health
10 Département de Génomes et Génétique - Department of Genomes and Genetics
11 University of Washington [Seattle]
12 University of Michigan [Ann Arbor]
13 UTHealth - The University of Texas Health Science Center at Houston
14 NIA - National Institute on Aging [Bethesda, USA]
15 UFPel - Universidade Federal de Pelotas = Federal University of Pelotas
16 USP - Universidade de São Paulo = University of São Paulo
17 Wake Forest University
18 BROAD INSTITUTE - Broad Institute of MIT and Harvard
19 LUMC - Leiden University Medical Center
20 Edin. - University of Edinburgh

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.

Domaines: Bio-informatique [q-bio.QM]; Méthodologie [stat.ME]; Applications [stat.AP]; Santé publique et épidémiologie; Génétique humaine

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⟩