학술논문
Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
Document Type
article
Author
Lisa de las Fuentes; Karen L. Schwander; Michael R. Brown; Amy R. Bentley; Thomas W. Winkler; Yun Ju Sung; Patricia B. Munroe; Clint L. Miller; Hugo Aschard; Stella Aslibekyan; Traci M. Bartz; Lawrence F. Bielak; Jin Fang Chai; Ching-Yu Cheng; Rajkumar Dorajoo; Mary F. Feitosa; Xiuqing Guo; Fernando P. Hartwig; Andrea Horimoto; Ivana Kolčić; Elise Lim; Yongmei Liu; Alisa K. Manning; Jonathan Marten; Solomon K. Musani; Raymond Noordam; Sandosh Padmanabhan; Tuomo Rankinen; Melissa A. Richard; Paul M. Ridker; Albert V. Smith; Dina Vojinovic; Alan B. Zonderman; Maris Alver; Mathilde Boissel; Kaare Christensen; Barry I. Freedman; Chuan Gao; Franco Giulianini; Sarah E. Harris; Meian He; Fang-Chi Hsu; Brigitte Kühnel; Federica Laguzzi; Xiaoyin Li; Leo-Pekka Lyytikäinen; Ilja M. Nolte; Alaitz Poveda; Rainer Rauramaa; Muhammad Riaz; Antonietta Robino; Tamar Sofer; Fumihiko Takeuchi; Bamidele O. Tayo; Peter J. van der Most; Niek Verweij; Erin B. Ware; Stefan Weiss; Wanqing Wen; Lisa R. Yanek; Yiqiang Zhan; Najaf Amin; Dan E. Arking; Christie Ballantyne; Eric Boerwinkle; Jennifer A. Brody; Ulrich Broeckel; Archie Campbell; Mickaël Canouil; Xiaoran Chai; Yii-Der Ida Chen; Xu Chen; Kumaraswamy Naidu Chitrala; Maria Pina Concas; Ulf de Faire; Renée de Mutsert; H. Janaka de Silva; Paul S. de Vries; Ahn Do; Jessica D. Faul; Virginia Fisher; James S. Floyd; Terrence Forrester; Yechiel Friedlander; Giorgia Girotto; C. Charles Gu; Göran Hallmans; Sami Heikkinen; Chew-Kiat Heng; Georg Homuth; Steven Hunt; M. Arfan Ikram; David R. Jacobs; Maryam Kavousi; Chiea Chuen Khor; Tuomas O. Kilpeläinen; Woon-Puay Koh; Pirjo Komulainen; Carl D. Langefeld; Jingjing Liang; Kiang Liu; Jianjun Liu; Kurt Lohman; Reedik Mägi; Ani W. Manichaikul; Colin A. McKenzie; Thomas Meitinger; Yuri Milaneschi; Matthias Nauck; Christopher P. Nelson; Jeffrey R. O’Connell; Nicholette D. Palmer; Alexandre C. Pereira; Thomas Perls; Annette Peters; Ozren Polašek; Olli T. Raitakari; Kenneth Rice; Treva K. Rice; Stephen S. Rich; Charumathi Sabanayagam; Pamela J. Schreiner; Xiao-Ou Shu; Stephen Sidney; Mario Sims; Jennifer A. Smith; John M. Starr; Konstantin Strauch; E. Shyong Tai; Kent D. Taylor; Michael Y. Tsai; André G. Uitterlinden; Diana van Heemst; Melanie Waldenberger; Ya-Xing Wang; Wen-Bin Wei; Gregory Wilson; Deng Xuan; Jie Yao; Caizheng Yu; Jian-Min Yuan; Wei Zhao; Diane M. Becker; Amélie Bonnefond; Donald W. Bowden; Richard S. Cooper; Ian J. Deary; Jasmin Divers; Tõnu Esko; Paul W. Franks; Philippe Froguel; Christian Gieger; Jost B. Jonas; Norihiro Kato; Timo A. Lakka; Karin Leander; Terho Lehtimäki; Patrik K. E. Magnusson; Kari E. North; Ioanna Ntalla; Brenda Penninx; Nilesh J. Samani; Harold Snieder; Beatrice Spedicati; Pim van der Harst; Henry Völzke; Lynne E. Wagenknecht; David R. Weir; Mary K. Wojczynski; Tangchun Wu; Wei Zheng; Xiaofeng Zhu; Claude Bouchard; Daniel I. Chasman; Michele K. Evans; Ervin R. Fox; Vilmundur Gudnason; Caroline Hayward; Bernardo L. Horta; Sharon L. R. Kardia; Jose Eduardo Krieger; Dennis O. Mook-Kanamori; Patricia A. Peyser; Michael M. Province; Bruce M. Psaty; Igor Rudan; Xueling Sim; Blair H. Smith; Rob M. van Dam; Cornelia M. van Duijn; Tien Yin Wong; Donna K. Arnett; Dabeeru C. Rao; James Gauderman; Ching-Ti Liu; Alanna C. Morrison; Jerome I. Rotter; Myriam Fornage
Source
Frontiers in Genetics, Vol 14 (2023)
Subject
Language
English
ISSN
1664-8021
Abstract
Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.