학술논문
Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits
Document Type
article
Author
Daokun Sun; Melissa A. Richard; Solomon K. Musani; Yun Ju Sung; Thomas W. Winkler; Karen Schwander; Jin Fang Chai; Xiuqing Guo; Tuomas O. Kilpeläinen; Dina Vojinovic; Hugues Aschard; Traci M. Bartz; Lawrence F. Bielak; Michael R. Brown; Kumaraswamy Chitrala; Fernando P. Hartwig; Andrea R.V.R. Horimoto; Yongmei Liu; Alisa K. Manning; Raymond Noordam; Albert V. Smith; Sarah E. Harris; Brigitte Kühnel; Leo-Pekka Lyytikäinen; Ilja M. Nolte; Rainer Rauramaa; Peter J. van der Most; Rujia Wang; Erin B. Ware; Stefan Weiss; Wanqing Wen; Lisa R. Yanek; Dan E. Arking; Donna K. Arnett; Ana Barac; Eric Boerwinkle; Ulrich Broeckel; Aravinda Chakravarti; Yii-Der Ida Chen; L. Adrienne Cupples; Martha L. Davigulus; Lisa de las Fuentes; Renée de Mutsert; Paul S. de Vries; Joseph A.C. Delaney; Ana V. Diez Roux; Marcus Dörr; Jessica D. Faul; Amanda M. Fretts; Linda C. Gallo; Hans Jörgen Grabe; C. Charles Gu; Tamara B. Harris; Catharina C.A. Hartman; Sami Heikkinen; M. Arfan Ikram; Carmen Isasi; W. Craig Johnson; Jost Bruno Jonas; Robert C. Kaplan; Pirjo Komulainen; Jose E. Krieger; Daniel Levy; Jianjun Liu; Kurt Lohman; Annemarie I. Luik; Lisa W. Martin; Thomas Meitinger; Yuri Milaneschi; Jeff R. O’Connell; Walter R. Palmas; Annette Peters; Patricia A. Peyser; Laura Pulkki-Råback; Leslie J. Raffel; Alex P. Reiner; Kenneth Rice; Jennifer G. Robinson; Frits R. Rosendaal; Carsten Oliver Schmidt; Pamela J. Schreiner; Lars Schwettmann; James M. Shikany; Xiao-ou Shu; Stephen Sidney; Mario Sims; Jennifer A. Smith; Nona Sotoodehnia; Konstantin Strauch; E. Shyong Tai; Kent D. Taylor; André G. Uitterlinden; Cornelia M. van Duijn; Melanie Waldenberger; Hwee-Lin Wee; Wen-Bin Wei; Gregory Wilson; Deng Xuan; Jie Yao; Donglin Zeng; Wei Zhao; Xiaofeng Zhu; Alan B. Zonderman; Diane M. Becker; Ian J. Deary; Christian Gieger; Timo A. Lakka; Terho Lehtimäki; Kari E. North; Albertine J. Oldehinkel; Brenda W.J.H. Penninx; Harold Snieder; Ya-Xing Wang; David R. Weir; Wei Zheng; Michele K. Evans; W. James Gauderman; Vilmundur Gudnason; Bernardo L. Horta; Ching-Ti Liu; Dennis O. Mook-Kanamori; Alanna C. Morrison; Alexandre C. Pereira; Bruce M. Psaty; Najaf Amin; Ervin R. Fox; Charles Kooperberg; Xueling Sim; Laura Bierut; Jerome I. Rotter; Sharon L.R. Kardia; Nora Franceschini; Dabeeru C. Rao; Myriam Fornage
Source
HGG Advances, Vol 2, Iss 1, Pp 100013- (2021)
Subject
Language
English
ISSN
2666-2477
Abstract
Summary: 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 five 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 and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations.