Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. / Adewuyi, Emmanuel O; Mehta, Divya; Sapkota, Yadav et al.

I: Human Genetics, Bind 140, Nr. 3, 03.2021, s. 529-552.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Adewuyi, EO, Mehta, D, Sapkota, Y, International Endogene Consortium (IEC), 23andMe Research Team, Auta, A, Yoshihara, K, Nyegaard, M, Griffiths, LR, Montgomery, GW, Chasman, DI & Nyholt, DR 2021, 'Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality', Human Genetics, bind 140, nr. 3, s. 529-552. https://doi.org/10.1007/s00439-020-02223-6

APA

Adewuyi, E. O., Mehta, D., Sapkota, Y., International Endogene Consortium (IEC), 23andMe Research Team, Auta, A., Yoshihara, K., Nyegaard, M., Griffiths, L. R., Montgomery, G. W., Chasman, D. I., & Nyholt, D. R. (2021). Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. Human Genetics, 140(3), 529-552. https://doi.org/10.1007/s00439-020-02223-6

CBE

Adewuyi EO, Mehta D, Sapkota Y, International Endogene Consortium (IEC), 23andMe Research Team, Auta A, Yoshihara K, Nyegaard M, Griffiths LR, Montgomery GW, et al. 2021. Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. Human Genetics. 140(3):529-552. https://doi.org/10.1007/s00439-020-02223-6

MLA

Vancouver

Adewuyi EO, Mehta D, Sapkota Y, International Endogene Consortium (IEC), 23andMe Research Team, Auta A et al. Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. Human Genetics. 2021 mar.;140(3):529-552. https://doi.org/10.1007/s00439-020-02223-6

Author

Adewuyi, Emmanuel O ; Mehta, Divya ; Sapkota, Yadav et al. / Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality. I: Human Genetics. 2021 ; Bind 140, Nr. 3. s. 529-552.

Bibtex

@article{f5de81e9e4d34d848e8a2c29cb899c4e,
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 (PFsig-permuted = 9.99 x 10(-4)). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (r(G) = 0.27,P = 8.85 x 10(-27)). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P <5 x 10(-8)), 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 combinedPvalue (FCPgene <2.75 x 10(-6)). Genes with a nominal gene-based association (P-gene <0.05) were significantly enriched across endometriosis and depression (Pbinomial-test = 2.90 x 10(-4)). Also, genes overlapping the two traits atP(gene) <0.1 (Pbinomial-test = 1.31 x 10(-5)) 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.",
keywords = "FACTORS CONTRIBUTE, GASTROESOPHAGEAL-REFLUX DISEASE, GENOME-WIDE ASSOCIATION, MAJOR DEPRESSION, MENDELIAN RANDOMIZATION, PELVIC PAIN, PROTON-PUMP INHIBITORS, QUALITY-OF-LIFE, WEB SERVER, WOMEN",
author = "Adewuyi, {Emmanuel O} and Divya Mehta and Yadav Sapkota and {International Endogene Consortium (IEC)} and {23andMe Research Team} and Asa Auta and Kosuke Yoshihara and Mette Nyegaard and Griffiths, {Lyn R} and Montgomery, {Grant W} and Chasman, {Daniel I} and Nyholt, {Dale R}",
year = "2021",
month = mar,
doi = "10.1007/s00439-020-02223-6",
language = "English",
volume = "140",
pages = "529--552",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Genetic analysis of endometriosis and depression identifies shared loci and implicates causal links with gastric mucosa abnormality

AU - Adewuyi, Emmanuel O

AU - Mehta, Divya

AU - Sapkota, Yadav

AU - International Endogene Consortium (IEC)

AU - 23andMe Research Team

AU - Auta, Asa

AU - Yoshihara, Kosuke

AU - Nyegaard, Mette

AU - Griffiths, Lyn R

AU - Montgomery, Grant W

AU - Chasman, Daniel I

AU - Nyholt, Dale R

PY - 2021/3

Y1 - 2021/3

N2 - 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 (PFsig-permuted = 9.99 x 10(-4)). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (r(G) = 0.27,P = 8.85 x 10(-27)). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P <5 x 10(-8)), 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 combinedPvalue (FCPgene <2.75 x 10(-6)). Genes with a nominal gene-based association (P-gene <0.05) were significantly enriched across endometriosis and depression (Pbinomial-test = 2.90 x 10(-4)). Also, genes overlapping the two traits atP(gene) <0.1 (Pbinomial-test = 1.31 x 10(-5)) 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.

AB - 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 (PFsig-permuted = 9.99 x 10(-4)). Linkage disequilibrium score regression (LDSC) analysis estimated a positive and highly significant genetic correlation between the two traits (r(G) = 0.27,P = 8.85 x 10(-27)). A meta-analysis of endometriosis and depression GWAS (sample size = 709,111), identified 20 independent genome-wide significant loci (P <5 x 10(-8)), 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 combinedPvalue (FCPgene <2.75 x 10(-6)). Genes with a nominal gene-based association (P-gene <0.05) were significantly enriched across endometriosis and depression (Pbinomial-test = 2.90 x 10(-4)). Also, genes overlapping the two traits atP(gene) <0.1 (Pbinomial-test = 1.31 x 10(-5)) 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.

KW - FACTORS CONTRIBUTE

KW - GASTROESOPHAGEAL-REFLUX DISEASE

KW - GENOME-WIDE ASSOCIATION

KW - MAJOR DEPRESSION

KW - MENDELIAN RANDOMIZATION

KW - PELVIC PAIN

KW - PROTON-PUMP INHIBITORS

KW - QUALITY-OF-LIFE

KW - WEB SERVER

KW - WOMEN

U2 - 10.1007/s00439-020-02223-6

DO - 10.1007/s00439-020-02223-6

M3 - Journal article

C2 - 32959083

VL - 140

SP - 529

EP - 552

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 3

ER -