Faculty, Staff and Student Publications

Authors

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

Publication Date

1-1-2023

Journal

Frontiers in Genetics

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.

Keywords

educational attainment, lipids, cholesterol, triglycerides, genome-wide association study, meta-analysis

DOI

10.3389/fgene.2023.1235337

PMID

38028628

PMCID

PMC10651736

PubMedCentral® Posted Date

November 2023

PubMedCentral® Full Text Version

Post-print

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