Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
32959083
TITLE
Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality.
ABSTRACT
Evidence from observational studies indicates that endometriosis and depression often co-occur. However, conflicting evidence exists, and the etiology as well as biological mechanisms underlying their comorbidity remain unknown. Utilizing genome-wide association study (GWAS) data, we comprehensively assessed the relationship between endometriosis and depression. Single nucleotide polymorphism effect concordance analysis (SECA) found a significant genetic overlap between endometriosis and depression (P  = 9.99 × 10 ). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (r  = 0.27, P = 8.85 × 10 ). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P < 5 × 10 ), of which eight are novel. Mendelian randomization analysis (MR) suggests a causal effect of depression on endometriosis. Combining gene-based association results across endometriosis and depression GWAS, we identified 22 genes with a genome-wide significant Fisher's combined P value (FCP  < 2.75 × 10 ). Genes with a nominal gene-based association (P  < 0.05) were significantly enriched across endometriosis and depression (P  = 2.90 × 10 ). Also, genes overlapping the two traits at P  < 0.1 (P  = 1.31 × 10 ) were significantly enriched for the biological pathways 'cell-cell adhesion', 'inositol phosphate metabolism', 'Hippo-Merlin signaling dysregulation' and 'gastric mucosa abnormality'. These results reveal a shared genetic etiology for endometriosis and depression. Indeed, additional analyses found evidence of a causal association between each of endometriosis and depression and at least one abnormal condition of gastric mucosa. Our study confirms the comorbidity of endometriosis and depression, implicates links with gastric mucosa abnormalities in their causal pathways and reveals potential therapeutic targets for further investigation.
DATE PUBLISHED
2020 Sep 21
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2020/05/21
accepted 2020/09/02
entrez 2020/09/22 05:43
pubmed 2020/09/23 06:00
medline 2020/09/23 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Adewuyi EO Adewuyi Emmanuel O EO School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia. emmanuel.adewuyi@qut.edu.au.
Mehta D Mehta Divya D School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
Sapkota Y Sapkota Yadav Y Department of Epidemiology And Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.
International Endogene Consortium
23andMe Research Team
Auta A Auta Asa A School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK.
Yoshihara K Yoshihara Kosuke K Department of Obstetrics And Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 950-2181, Japan.
Nyegaard M Nyegaard Mette M iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 2100, Copenhagen, Denmark.
Griffiths LR Griffiths Lyn R LR School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Chasman DI Chasman Daniel I DI Divisions of Preventive Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Nyholt DR Nyholt Dale R DR School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, QLD, Australia. d.nyholt@qut.edu.au.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Sapkota Yadav Y
Yoshihara Kosuke K
Nyegaard Mette M
Steinthorsdottir Valgerdur V
Morris Andrew P AP
Fassbender Amelie A
Rahmioglu Nilufer N
De Vivo Immaculata I
Buring Julie E JE
Zhang Futao F
Edwards Todd L TL
Jones Sarah S
Dorien
Peterse Daniëlle D
Rexrode Kathryn M KM
Ridker Paul M PM
Schork Andrew J AJ
MacGregor Stuart S
Martin Nicholas G NG
Becker Christian M CM
Adachi Sosuke S
Enomoto Takayuki T
Takahashi Atsushi A
Kamatani Yoichiro Y
Matsuda Koichi K
Kubo Michiaki M
Thorleifsson Gudmar G
Geirsson Reynir T RT
Thorsteinsdottir Unnur U
Wallace Leanne M LM
Yang Jian J
Velez Edwards Digna R DR
Nyegaard Mette M
Low Siew-Kee SK
Zondervan Krina T KT
Missmer Stacey A SA
D'Hooghe Thomas T
Stefansson Kari K
Tung Joyce Y JY
Montgomery Grant W GW
Chasman Daniel I DI
Nyholt Dale R DR
Agee Michelle M
Alipanahi Babak B
Auton Adam A
Bell Robert K RK
Bryc Katarzyna K
Elson Sarah L SL
Fontanillas Pierre P
Furlotte Nicholas A NA
Huber Karen E KE
Kleinman Aaron A
Litterman Nadia K NK
McIntyre Matthew H MH
Mountain Joanna L JL
Noblin Elizabeth S ES
Northover Carrie A M CAM
Pitts Steven J SJ
Fah Sathirapongsasuti J J
Sazonova Olga V OV
Shelton Janie F JF
Shringarpure Suyash S
Tian Chao C
Vacic Vladimir V
Wilson Catherine H CH
JOURNAL
VOLUME:
ISSUE:
TITLE: Human genetics
ISOABBREVIATION: Hum. Genet.
YEAR: 2020
MONTH: Sep
DAY: 21
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1432-1203
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Genet
COUNTRY: Germany
ISSNLINKING: 0340-6717
NLMUNIQUEID: 7613873
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
241,944, 339,462, 389,927, 389,875, 389,891, 389,892, 389,938, 443,036, 442,915, 442,981, 496,610, 496,739, 552,485, 552,498, 1,026,033 National Health and Medical Research Council (AU)
1,050,208 National Health and Medical Research Council (AU)
076113 Wellcome Trust United Kingdom
085475 Wellcome Trust United Kingdom
R102-A9118 The Lundbeck Foundation, Denmark
R155-2014-1724 The Lundbeck Foundation, Denmark
GENERAL NOTE
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