Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci
Nenhuma Miniatura disponível
Citações na Scopus
0
Tipo de produção
article
Data de publicação
2023
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
FUENTES, Lisa de las
SCHWANDER, Karen L. M.
BROWN, Michael R.
BENTLEY, Amy R.
WINKLER, Thomas W.
SUNG, Yun Ju
MUNROE, Patricia B.
MILLER, Clint L.
ASCHARD, Hugo
ASLIBEKYAN, Stella
Citação
FRONTIERS IN GENETICS, v.14, article ID 1235337, 16p, 2023
Resumo
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 x 10(-8)) and suggestive (p < 1 x 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.
Palavras-chave
educational attainment, lipids, cholesterol, triglycerides, genome-wide association study, meta-analysis
Referências
- Ahima RS, 2006, OBESITY, V14, P242, DOI 10.1038/oby.2006.317
- Altshuler DM, 2012, NATURE, V491, P56, DOI 10.1038/nature11632
- Assari Shervin, 2019, Hosp Pract Res, V4, P86, DOI 10.15171/HPR.2019.17
- Assary E, 2018, SEMIN CELL DEV BIOL, V77, P133, DOI 10.1016/j.semcdb.2017.10.016
- Bacon C, 2012, HUM GENET, V131, P1687, DOI 10.1007/s00439-012-1193-z
- Baigent C, 2005, LANCET, V366, P1267, DOI 10.1016/S0140-6736(05)67394-1
- Bays HE, 2013, J CLIN LIPIDOL, V7, P304, DOI 10.1016/j.jacl.2013.04.001
- Blockus H, 2014, CURR OPIN NEUROBIOL, V27, P82, DOI 10.1016/j.conb.2014.03.003
- Braveman PA, 2005, JAMA-J AM MED ASSOC, V294, P2879, DOI 10.1001/jama.294.22.2879
- Cao XH, 2007, EUR J NEUROSCI, V25, P1815, DOI 10.1111/j.1460-9568.2007.05431.x
- Cooke PS, 2007, OBESITY, V15, P1400, DOI 10.1038/oby.2007.168
- de las Fuentes L, 2021, MOL PSYCHIATR, V26, P2111, DOI 10.1038/s41380-020-0719-3
- Devlin B, 1999, BIOMETRICS, V55, P997, DOI 10.1111/j.0006-341X.1999.00997.x
- Dietschy JM, 2001, CURR OPIN LIPIDOL, V12, P105, DOI 10.1097/00041433-200104000-00003
- Santo LRE, 2022, INT HEALTH, V14, P346, DOI 10.1093/inthealth/ihz089
- Fedele L, 2018, NAT COMMUN, V9, DOI 10.1038/s41467-018-02927-4
- Franssen R, 2011, MED CLIN N AM, V95, P893, DOI 10.1016/j.mcna.2011.06.003
- FRIEDEWALD WT, 1972, CLIN CHEM, V18, P499
- Gallo LC, 2001, PSYCHOSOM MED, V63, P925, DOI 10.1097/00006842-200111000-00011
- Gliozzi M, 2021, PHARMACOL RES, V163, DOI 10.1016/j.phrs.2020.105215
- Gnudi L, 1996, AM J PHYSIOL-REG I, V270, pR785, DOI 10.1152/ajpregu.1996.270.4.R785
- Graham SJL, 2009, DIFFERENTIATION, V77, P239, DOI 10.1016/j.diff.2008.10.013
- Hamad R, 2019, PLOS MED, V16, DOI 10.1371/journal.pmed.1002834
- Jung UJ, 2014, INT J MOL SCI, V15, P6184, DOI 10.3390/ijms15046184
- Kamm GB, 2013, MOL BIOL EVOL, V30, P1088, DOI 10.1093/molbev/mst023
- KAPLAN GA, 1993, CIRCULATION, V88, P1973, DOI 10.1161/01.CIR.88.4.1973
- Kavousi M., 2022, medRxiv, DOI [10.1101/2022.05.02.22273844v1, DOI 10.1101/2022.05.02.22273844V1, DOI 10.1101/2022.05.02.22273844]
- Kraft P, 2007, HUM HERED, V63, P111, DOI 10.1159/000099183
- Krycer JR, 2017, FEBS LETT, V591, P322, DOI 10.1002/1873-3468.12549
- Kushnireva L, 2021, FRONT SYNAPTIC NEURO, V12, DOI 10.3389/fnsyn.2020.573714
- Ledreux A, 2016, BEHAV BRAIN RES, V312, P294, DOI 10.1016/j.bbr.2016.06.012
- Leino M, 1999, INT J EPIDEMIOL, V28, P667, DOI 10.1093/ije/28.4.667
- Leng B, 2015, J HYPERTENS, V33, P221, DOI 10.1097/HJH.0000000000000428
- Li SN, 2020, NAT METAB, V2, P1077, DOI 10.1038/s42255-020-00289-0
- Liu P, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-12988-8
- Loriol C, 2013, BIOL CELL, V105, P30, DOI 10.1111/boc.201200016
- LoTurco JJ, 2006, TRENDS NEUROSCI, V29, P407, DOI 10.1016/j.tins.2006.05.006
- Majewski L, 2017, BBA-MOL CELL RES, V1864, P1071, DOI 10.1016/j.bbamcr.2016.11.025
- Manning AK, 2011, GENET EPIDEMIOL, V35, P11, DOI 10.1002/gepi.20546
- Matsuda S, 2009, J BIOL CHEM, V284, P15815, DOI 10.1074/jbc.M109.006403
- MATTHEWS KA, 1989, AM J EPIDEMIOL, V129, P1132, DOI 10.1093/oxfordjournals.aje.a115235
- Melbourne CA, 2022, ENVIRON INT, V159, DOI 10.1016/j.envint.2021.107041
- Metcalf PA, 1998, AM J EPIDEMIOL, V148, P750
- Miao L, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-10950-6
- Okada M, 2009, BIOCHEM BIOPH RES CO, V379, P249, DOI 10.1016/j.bbrc.2008.12.069
- Okbay A, 2016, NATURE, V533, P539, DOI 10.1038/nature17671
- Peloso GM, 2014, AM J HUM GENET, V94, P223, DOI 10.1016/j.ajhg.2014.01.009
- Perera HKI, 2003, MOL BIOL CELL, V14, P2946, DOI 10.1091/mbc.E02-11-0722
- Pistell PJ, 2010, J NEUROIMMUNOL, V219, P25, DOI 10.1016/j.jneuroim.2009.11.010
- Pradhan G, 2013, CURR OPIN CLIN NUTR, V16, P619, DOI 10.1097/MCO.0b013e328365b9be
- Rao DC, 2017, CIRC-CARDIOVASC GENE, V10, DOI 10.1161/CIRCGENETICS.116.001649
- Romero A, 2010, EUR J ENDOCRINOL, V163, P1, DOI 10.1530/EJE-10-0099
- Scherer T, 2016, DIABETES, V65, P1511, DOI 10.2337/db15-1552
- Sémon M, 2006, MOL BIOL EVOL, V23, P1715, DOI 10.1093/molbev/msl034
- SHEA S, 1993, PREV MED, V22, P203, DOI 10.1006/pmed.1993.1017
- Shulman GI, 2014, NEW ENGL J MED, V371, P1131, DOI 10.1056/NEJMra1011035
- SOREL JE, 1992, AM J EPIDEMIOL, V135, P1339, DOI 10.1093/oxfordjournals.aje.a116245
- Sung YJ, 2015, AM J HYPERTENS, V28, P343, DOI [10.1093/ajh/hpu149, 10.1093/ajh/hpt283]
- Swanger SA, 2016, AM J HUM GENET, V99, P1261, DOI 10.1016/j.ajhg.2016.10.002
- Tamaki K, 2008, NEUROSCI LETT, V433, P183, DOI 10.1016/j.neulet.2007.12.062
- Tyroler H. A., 1989, Hypertension, V13, pI94, DOI [DOI 10.1161/01.HYP.13.5_SUPPL.I94, DOI 10.1161/01.HYP.13.5_Suppl.I94]
- Wang H, 2009, AM J PHYSIOL-ENDOC M, V297, pE271, DOI 10.1152/ajpendo.90920.2008
- Wang K, 2010, NUCLEIC ACIDS RES, V38, DOI 10.1093/nar/gkq603
- Ward LD, 2012, NUCLEIC ACIDS RES, V40, pD930, DOI 10.1093/nar/gkr917
- Watanabe K, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-01261-5
- Werme J, 2021, TRANSL PSYCHIAT, V11, DOI 10.1038/s41398-021-01288-9
- Willer CJ, 2010, BIOINFORMATICS, V26, P2190, DOI 10.1093/bioinformatics/btq340
- Woo JMP, 2022, J INTERN MED, V291, P755, DOI 10.1111/joim.13448
- Xu Q, 2012, FEBS LETT, V586, P1803, DOI 10.1016/j.febslet.2012.05.018
- Yang L, 2015, INT J CLIN EXP PATHO, V8, P10725
- Yi CX, 2012, DIS MODEL MECH, V5, P583, DOI 10.1242/dmm.009902
- Zhang YQ, 2018, NEUROSCIENCE, V371, P207, DOI 10.1016/j.neuroscience.2017.12.001
- Zhou Y, 2014, J NEURAL TRANSM, V121, P799, DOI 10.1007/s00702-014-1180-8
- Zou YK, 2015, J BIOL CHEM, V290, P30607, DOI 10.1074/jbc.M115.681627