Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing
Abstract
:1. Introduction
1.1. Epidemiology and Phenotypic Description
1.2. Diagnosis
1.3. Origin and Genetics
2. Procedure of This Review for the GWAS and Overview of the Results
3. Genome-wide Association Studies
3.1. Large GWAS from Heterogeneous Populations
3.2. GWAS Studies from Genetic Isolates
3.3. Small-scale GWAS and Pooling Approaches
3.4. Genetic Connections between Endometriosis and Other Diseases and Phenotypes
3.5. Genetic Regulation of Gene Expression and System Biology Analyses in Connection with GWAS Approaches
4. Replication Studies
5. Functional Studies
- In endometriosis, as in many complex diseases, there is a discrepancy between the calculated heritability and the sum of the SNP effects found in GWAS. This difference is explained by the concept of missing heritability [88]. More precisely, it has been estimated in 2012 that the total variation tagged by frequent SNPs as used in GWAS was 0.26, i.e., about half of the total genetic variation [55]. Missing heritability is currently explained by various hypotheses, one of the most prominent relies in the idea that GWAS are carried out using microarray platforms encompassing SNPs having a relatively high Minor Allele Frequency (MAF) and hence, will miss rare alleles that may be the one indeed associated to the disease. These rare alleles have presumably been counter-selected through the mechanisms of evolution. An indication of such possibility is provided in [41], where the authors focused on protein modifying variants analyzing 7164 cases and 21,005 controls for the discovery and 1840 cases and 129,016 controls in the replication cohort. The only locus that was replicated was GREB1 at2p25. Even in exome arrays designs, rare variants are not massively present, which could explain this relative failure. The authors logically conclude that sequencing high-risk families at the exome level is a promising way to identify novel rare variants in genes involved in endometriosis. Another major issue is the impact of inter-patient variability in the big GWAS approaches, suggesting that optimizing the clinical classification of the patients could improve the detection power of the GWAS [89,90]. Other explanations are the possible association of disease with CNVs (variations in length of large repeats), which are poorly addressed by classical arrays, epigenetics regulation that may also mask some of the gene-defined variation, as well as epistatic mechanisms that implies that for obtaining a tangible phenotype, the co-occurrence of two or more gene variants is requested [91].
- Finding a significant SNPs does not explain how, functionally, this SNP triggers the disease risk, the situation being made even more difficult because the relative risk is generally comprised between 1.1 and 1.5, meaning that many carriers of the ‘at-risk’ variant are not stricken by the disease, while carriers of the ‘protective’ variant are not at all. This latest question was systematically addressed in a 2015 review by Fung and co-workers, and showed that once the variant is identified, a long and tedious stroll commences, from a refined mapping with additional SNPs in the region identified, a study of existing functional annotations (which is difficult when non-coding or intergenic SNPs are found, a case encountered for the chromosome 7 rs12700667 in endometriosis ), a measure of cell-type specific gene expression and protein levels, analysis of the cell-type specific local epigenetic regulation, cell models and animal models, eventually, if available, a complicated issue in the case of a human-specific disease such as endometriosis [92].
6. Exome Sequencing
6.1. Family Studies
6.2. Population Studies
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
References
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REFERENCE | PAPER PMID | ETHNICITY | STUDY TYPE | CASES (N) | CONTROLS (N) | ENDOME TRIOSIS DIAGNOSIS | CONTROLS SELECTION | STAGES OF THE STUDY | ASSOCIATED SNPs | SNP NAMES |
---|---|---|---|---|---|---|---|---|---|---|
(a) Discovery Study | ||||||||||
Uno et al., 2010 [30] | 20601957 | Asian | Case-control of hospital based | 1907 | 5292 | Laparoscopy | Laparoscopy | Discovery | 1 | rs10965235 (CDKN2BAS) |
Adachi et al., 2010 [31] | 20844546 | Asian | Meta-analysis of population and hospital based | 696 | 825 | Medical history, MRI and laparoscopy | Medical history, MRI and laparoscopy | Discovery | 5 | rs6542095, rs11677416, rs3783550 and rs3783525 (near IL1 A gene) and rs801112 (RHOU) |
Painter et al., 2011 [32] | 3019124 | Oceania and European | Meta-analysis of population and hospital based | 3194 | 7060 | Laparoscopy | Men, medical history and laparoscopy | Discovery | 1 | rs12700667 (NFE2L3-HOXA10) |
Nyholt et al., 2012 [33] | 23104006 | Oceania and European | Meta-analysis of population and hospital based | 4604 | 9393 | Laparoscopy | Men, medical history and laparoscopy | Discovery | 7 | rs12700667 (NFE2L3-HOXA10 ), rs75211902 (WNT4), rs1537377 (CDKN2B-AS1), rs10859871 (VEZT), rs4141819 (ETAA1), rs77399264 (ID4), rs13394619 (GREB1) |
Pagliardini et al., 2013 [34] | 23142796 | Asian and European | Meta-analysis of population and hospital based | 305 | 2710 | Laparoscopy | Laparoscopy blood donors | Discovery | 3 | rs1333049 (CDKN2BAS), rs7521902 (WNT4), rs1250248 (FN1) |
Albertsen et al., 2013 [35] | 23472165 | European | Case-control of hospital base | 2019 | 14,471 | Laparoscopy | Laparoscopy | Discovery | 3 | rs2235529 (LINC00339-WNT4),rs1519761 and rs6757804 (RND3) |
Rahmioglu et al., 2014 [36] | 24676469 | American, European and Oceania | Meta-analysis of population and hospital based | 11,506 | 32,678 | Laparoscopy | Laparoscopy | Discovery | 6 | rs12700667 (NFE2L3-HOXA10),rs7521902 (WNT4), rs10859871 (VEZT) rs1537377 (CDKN2B-AS1), rs7739264 (ID4), rs13394619 (GREB1) |
Borghese et al., 2015 [37] | 25722978 | European | Meta-analysis of population and hospital based | 60 | 20 | Laparoscopy | Laparoscopy | Discovery | 4 | rs4703908 (ZNF366),rs227849 (RUNX2/ SUPT3H), rs2479037 (VTI1A) and rs966674 (NA) |
Sapkota et al., 2015 [38] | 26337243 | Asian, African, European and Oceania | Meta-analysis of population and hospital-based | 998 | 783 | Laparoscopy | Laparoscopy | Discovery | 6 | rs7521902 (WNT4), rs13394619 in GREB1, rs12700667 (NFE2L3-HOXA10), rs6542095 (IL1A, rs7739264 (ID4) and rs1537377 (CDKN2B-AS1) |
Wang et al., 2016 [39] | 27506219 | Asian | Case-control of hospital based | 1448 | 1540 | Laparoscopy | Laparoscopy | Discovery | 3 | rs11692361 (MEIS1), rs10256972 (C7orf50), rs4966038 (IGF-1R) |
Uimari et al., 2017 [40] | 28333195 | Oceania and European | Case-control of hospital-based | 3194 | 7060 | Laparoscopy | Men, medical history and laparoscopy | Discovery | 1 | rs144240142 (MAP3K4) |
Sapkota et al., 2017 [41] | 28537267 | Asian, Oceania European and American | Meta-analysis of population and hospital-based | 17,045 | 191,596 | Laparoscopy | Medical history and laparoscopy | Discovery | 19 | rs12037376 (WNT4), rs11674184 and rs77294520 (GREB1), rs6546324 ( ETAA1), rs4762326 (VEZT), rs10167914 (IL1A), rs1903068 (KDR), rs760794 (ID4),rs74485684 (FSHB), rs12700667 (NFE2L3-HOXA10), rs1537377, rs1075727 and rs1448792 (CDKN2B-AS1), rs1250241 (FN1), rs1971256 (CCDC170), rs71575922 and rs17803970 (SYNE1) rs2206949 (ESR1), rs74491657 (7p12.3) |
Sobalska-kwapis et al., 2017 [42] | 28881265 | European | Case-control of hospital based | 171 | 2934 | Laparoscopy | Medical History | Discovery | 19 | 18 SNPs (near of C2)and rs10129516 (PARP1P2-RHOJ) |
Sapkota et al., 2017 [43] | 28900119 | Oceania, European and American | Meta-analysis of population and hospital based | 9000 | 150,001 | Medical History Laparoscopy | Medical History and Laparoscopy | Discovery | 3 | rs13394619 (GREB1 at 2p25.1), rs1801262 (CUBN), gene-level (CIITA et PARP4) |
Painter et al., 2018 [44] | 29608257 | European | Case-control of hospital based | 3194 | 2057 | Laparoscopy | Laparoscopy | Discovery | 13 | rs2475335 (PTRD), rs9865110 (PDZRN3-CNTN3), rs2278868 (SKAP1), rs12303900 (KITLG-DUSP6) rs9349553(TFAP2D), rs10008492 (KLF3-TLR10), rs9530566 (LMO7-KCTD12), rs17693745 (CEP112), rs1755833 (PRIM2), rs7515106 (WNT4-ZBTB40), rs10459129 (PARP11-CCND2) rs2198894 (ZNF536-TSHZ3), rs7042500 (THEM215-APTX) |
Christofolini et al., 2019 [45] | 30044155 | European | Case-control of hospital based | 394 | 650 | Laparoscopy | Laparoscopy | Discovery | 2 | rs10928050 (KAZN) and rs2427284 (LAM5) |
Adewuyi et al., 2020 [46] | 32121467 | European, Asian and American | Meta-analysis of population and hospital based | 76,728 | 507,936 | Medical history and laparoscopy | Medical History | Discovery | 3 | SNPs nears ARL14EP , TRIM32, and SLC35G6 |
(b) Replication Study | ||||||||||
Painter et al., 2011 [32] | 3019124 | Oceanie | Meta-analysis of population and hospital based | 2392 | 2271 | Laparoscopy | Men, medical history and laparoscopy | Replication | 1 | rs12700667 (NFE2L3-HOXA10) |
Nyholt et al., 2012 [33] | 23104006 | Asian Oceanie | Meta-analysis of population and hospital based | 1044 | 4017 | Laparoscopy | Men, medical history and laparoscopy | Replication | 7 | rs12700667 (NFE2L3-HOXA10 ), rs75211902 (WNT4), rs1537377 (CDKN2B-AS1), rs10859871 (VEZT),rs4141819 (ETAA1), rs77399264 (ID4), rs13394619 (GREB1) |
Albertsen et al., 2013 [35] | 23472165 | European | Meta-analysis of population and hospital based | 505 | 1811 | Laparoscopy | Laparoscopy | Replication | 3 | rs2235529 (LINC00339-WNT4),rs1519761 and rs6757804 (RND3) |
Sapkota et al., 2015 [38] | 26337243 | Asian, African | Meta-analysis of population and hospital based | 998 | 783 | Laparoscopy | Laparoscopy | Replication | 6 | rs7521902 (WNT4), rs13394619 in GREB1 rs12700667 (NFE2L3-HOXA10) |
Osiński et al., 2018 [47] | 30010178 | European | Case-control of hospital base | 315 | 406 | Laparoscopy | Medical History | Replication | 2 | rs12700667 (NFE2L3-HOXA10) and rs4141819 (ETAA1) |
(c) Connection between Endometriosis and Others Pathologies | ||||||||||
Painter et al., 2011 [32] | 3019124 | Oceanie and European | Meta-analysis of population and hospital based | 3194 | 7060 | Laparoscopy | Men, medical history and laparoscopy | Discovery | 1 | rs12700667 (NFE2L3-HOXA10) |
Gallagher et al., 2019 [48] | 31649266 | European | Case-control of hospital base | 35,474 | 267,505 | Medical history, MRI | Medical history, MRI | Discovery | 4 | rs58415480 (ESR1), rs11031006 (FSHB), rs35417544 (GREB1), rs7412010 (WNT4) |
Adewuyi et al., 2020 [46] | 32959083 | European, Asian and Americanian | Meta-analysis of population and hospital based | 187,810 | 521,301 | Laparoscopy | Medical History and laparoscopy | Discovery | 26 | rs116810322 (TRIM26), rs11793648 (TRIM32), rs9891297 (SLC35G6), rs1395455 (CSF3R), rs1620977 (NEGR1), rs12121863 (CRB1), rs9586 (KLHDC8B), rs9835157 (IP6K1), rs12512642 ( SCLT1), rs13164188 (NUDT12), rs7933594 (TYR), rs6680839 (TNR), rs72740410 (BRINP3), rs13118306 (CC2D2A), rs2134025 (TACR3) rs9347896 (C6orf1), rs11784932 (GSDMC), rs9538160 (PCDH17), rs35625885 (NR2F2), rs6808036 (CCDC36), rs323509 (NUDT12), rs6788293 (LINC00620) |
Locus | Gene(s) of Interest | SNP | Cases (N) | Controls (N) | RA | OA | Relative Risk | p-Value | Paper PMID |
---|---|---|---|---|---|---|---|---|---|
1p31.1 | NEGR1 | rs1620977 | 187,810 | 521,301 | A | G | 1.027 | 10−8 (10−2) * | 32959083 |
1p34.3 | CSF3R | rs1395455 | 187,810 | 521,301 | A | G | 1.025 | 10−8 (10−2) * | 32959083 |
1p36.12 | WNT4 | rs7521902 | 305 | 2710 | A | C | 1.2 | 10−9 | 23142796 |
rs7521902 | 11,506 | 32,678 | A | C | 1.18 | 10−15 | 24676469 | ||
rs4654783 | 2019 | 14,471 | A | G | 1.21 | 10−9 | 23472165 ** | ||
rs2235529 | 2019 | 14,471 | A | G | 1.29 | 10−9 | 23472165 ** | ||
rs7521902 | 4604 | 9393 | A | C | 1.18 | 10−8 | 23104006 | ||
rs7521902 | 1044 | 4017 | A | C | NA | 10−5 | 23104006 ** | ||
rs7521902 | 998 | 783 | A | C | 1.18 | 10−8 | 26337243 | ||
rs7521902 | 998 | 783 | A | C | 1.3 | 10−3 | 26337243 ** | ||
rs7521902 | 23,671 | 68,894 | A | C | 1.29 | 10−15 | 27470151 | ||
rs7739264 | 998 | 783 | T | C | 1.14 | 10−7 | 26337243 | ||
rs7515106 | 3194 | 2057 | C | T | 1.09 | 10−5 | 29608257 ** | ||
rs12037376 | 17,045 | 191,596 | A | G | 1.16 | 10−17 | 28537267 | ||
rs7412010 | 35,474 | 267,505 | C | G | 1.13 | 10−29 | 31649266 | ||
1p36.21 | KAZN | rs10928050 | 394 | 650 | A | G | 1.31 | 10−2 | 30044155 ** |
1q25.1 | TNR | rs6680839 | 187,810 | 521,301 | T | C | 0.975 | 10−10 (10−4) * | 32959083 |
1q31.1 | BRINP3 | rs72740410 | 187,810 | 521,301 | T | C | 1.048 | 10−8 (10−2) * | 32959083 |
1q31.3 | CRB1 | rs12121863 | 187,810 | 521,301 | A | T | 0.971 | 10−8 (10−2) * | 32959083 |
1q42.13 | RHOU | rs801112 | 696 | 825 | A | T | 1.65 | 10−6 | 20844546 |
2p14 | ETAA1 | rs6546324 | 998 | 191,596 | A | C | 1.08 | 10−9 | 28537267 |
rs4141819 | 4604 | 9393 | C | T | 1.15 | 10−8 | 23104006 | ||
rs4141819 | 1044 | 4017 | C | T | NA | 10−2 | 23104006 ** | ||
rs4141819 | 11,506 | 32,678 | C | T | 1.08 | 10−6 | 24676469 | ||
rs4141819 | 315 | 406 | C | T | 1.35 | 10−2 | 30010178 ** | ||
2p14 | MEIS1 | rs11692361 | 1448 | 1540 | C | T | 0.70 | 10−7 | 27506219 |
2p25.1 | GREB1 | rs13394619 | 11,506 | 32,678 | G | A | 1.13 | 10−8 | 24676469 |
rs13394619 | 998 | 783 | G | A | 1.15 | 10−9 | 26337243 | ||
rs13394619 | 998 | 783 | G | A | 1.13 | 10−2 | 26337243 ** | ||
rs13394619 | 7164 | 21,005 | A | G | 0.89 | 10−9 | 28900119 | ||
rs13394619 | 4604 | 9393 | A | G | 1.15 | 10−8 | 23104006 | ||
rs13394619 | 1044 | 4017 | A | G | NA | 10−3 | 23104006 ** | ||
rs11674184 | 17,045 | 191,596 | T | G | 1.13 | 10−17 | 28537267 | ||
rs77294520 | 17,045 | 191,596 | C | G | 1.16 | 10−13 | 28537267 | ||
rs35417544 | 35,474 | 267,505 | T | C | 1.09 | 10−13 | 31649266 | ||
2q13 | IL1A | rs6542095 | 696 | 825 | C | T | 1.5 | 10−6 | 20844546 |
rs6542095 | 998 | 783 | C | T | 1.22 | 10−10 | 26337243 ** | ||
rs6542095 | 998 | 783 | C | T | 1.26 | 10−2 | 26337243 | ||
rs6542095 | 7164 | 21,005 | T | C | 0.90 | 10−7 | 28900119 | ||
rs11677416 | 696 | 825 | T | A | 2.0 | 10−6 | 20844546 | ||
rs10167914 | 17,045 | 191,596 | G | A | 1.15 | 10−9 | 28537267 | ||
rs3783550 | 696 | 825 | C | A | 1.51 | 10−6 | 20844546 | ||
rs3783525 | 696 | 825 | A | T | 1.52 | 10−6 | 20844546 | ||
2q23.3 | RND3 | rs1519761 | 2019 | 14,471 | C | A | 1.20 | 10−7 | 23472165 ** |
rs6734792 | 2019 | 14,471 | G | A | 1.20 | 10−8 | 23472165 ** | ||
rs1519761 | 2019 | 14,471 | G | A | 1.20 | 10−8 | 23472165 ** | ||
rs6757804 | 2019 | 14,471 | G | A | 1.20 | 10−8 | 23472165 ** | ||
rs6734792 | 11,506 | 32,678 | C | T | 1.10 | 10−6 | 24676469 | ||
2q35 | FN1 | rs1250241 | 17,045 | 191,596 | T | A | 1.23 | 10−9 | 28537267 |
rs1250248 | 305 | 2710 | A | G | 1.13 | 10−9 | 23142796 | ||
rs1250248 | 1129 | 831 | A | G | 1.17 | 10−2 | 23315067 ** | ||
rs1250248 | 11,506 | 32,678 | A | G | 1.11 | 10−4 | 24676469 | ||
3p13-3p12.3 | PDZRN3-CNTN3 | rs9865110 | 3194 | 2057 | C | A | 1.1 | 10−6 | 29608257 |
3p21.31 | KLHDC8B | rs9586 | 187,810 | 521,301 | T | C | 0.976 | 10−8 (10−4) * | 32959083 |
3p21.31 | IP6K1 | rs9835157 | 187,810 | 521,301 | A | G | 1.034 | 10−8 (10−4) * | 32959083 |
3p21.31 | CCDC36 | rs6808036 | 187,810 | 521,301 | T | G | 1.044 | 10−8 (10−5) * | 32959083 |
3p25.1 | LINC00620 | rs6788293 | 187,810 | 521,301 | T | C | 0.952 | 10−8 (10−2) * | 32959083 |
4p14 | KLF3-TLR10 | rs10008492 | 3194 | 2057 | T | C | 1.14 | 10−5 | 29608257 |
4p15.32 | CC2D2A | rs13118306 | 187,810 | 521,301 | C | G | 0.977 | 10−8 (10−3) * | 32959083 |
4q12 | KDR | rs1903068 | 17,045 | 191,596 | A | G | 1.11 | 10−15 | 28537267 |
4q24 | TACR3 | rs2134025 | 187,810 | 521,301 | A | G | 1.029 | 10−8 (10−4) * | 32959083 |
4q28.2 | SCLT1 | rs12512642 | 187,810 | 521,301 | T | C | 1.28 | 10−8 (10−2) * | 32959083 |
5 | NA | rs966674 | 288 | 259 | C | G | 2.95 | 10−3 | 25722978 |
5q13.1 | ZNF366 | rs4703908 | 288 | 259 | C | G | 2.22 | 10−3 | 25722978 |
5q21.2 | NUDT12 | rs13164188 | 187,810 | 521,301 | T | C | 1.025 | 10−9 (10−2) * | 32959083 |
5q21.2 | NUDT12 | rs323509 | 187,810 | 521,301 | A | C | 1.042 | 10−8 (10−2) * | 32959083 |
6p11.2 | PRIM2 | rs1755833 | 3194 | 2057 | A | G | 0.93 | 10−5 | 29608257 |
6p12.3 | TFAP2D | rs9349553 | 3194 | 2057 | T | C | 1.09 | 10−6 | 29608257 |
6p21.1 | RUNX2/SUPT3H | rs227849 | 288 | 259 | A | G | 2.31 | 10−3 | 25722978 |
6p21.33 | C2 | rs644045 | 171 | 2934 | T | C | 1.90 | 10−10 | 28881265 |
6p22.1 | TRIM26 | rs116810322 | 187,810 | 521,301 | T | C | 1.042 | 10−9 (10−5) | 32959083 |
6p22.3 | ID4 | rs7739264 | 11,506 | 32,678 | T | C | 1.11 | 10−10 | 24676469 |
rs7739264 | 4604 | 9393 | T | C | 1.17 | 10−7 | 23104006 | ||
rs7739264 | 1044 | 4017 | T | C | NA | 10−4 | 23104006 ** | ||
rs7739264 | 998 | 783 | T | C | 1.14 | 10−7 | 26337243 | ||
rs7739264 | 23,671 | 68,894 | T | C | 1.10 | 10−10 | 27470151 | ||
rs760794 | 17,045 | 191,596 | T | C | 1.17 | 10−7 | 28537267 | ||
rs6907340 | 2019 | 14,471 | A | G | 1.12 | 10−7 | 23472165 | ||
6q12 | ESY | rs12206488 | 187,810 | 521,301 | A | G | 0.976 | 10−9 (10−3) * | 32959083 |
6q24.2 | HIVEP2 | rs2328370 | 187,810 | 521,301 | A | C | 1.023 | 10−9 (10−3) * | 32959083 |
6q25.1 | CCDC170 | rs1971256 | 17,045 | 191,596 | C | T | 1.09 | 10−8 | 28537267 |
6q25.1 | SYNE1 | rs71575922 | 17,045 | 191,596 | G | C | 1.11 | 10−8 | 28537267 |
rs17803970 | 17,045 | 191,596 | A | T | 1.15 | 10−8 | 28537267 | ||
6q25.1-q25.2 | ESR1 | rs2206949 | 17,045 | 191,596 | T | C | 1.10 | 10−7 | 28537267 |
rs58415480 | 35,474 | 267,505 | C | G | 1.19 | 10−7 | 31649266 | ||
6q26 | MAP3K4 | rs144240142 | 3194 | 7060 | T | C | 1.71 | 10−8 | 28333195 |
6q27 | C6orf1 | rs9347896 | 187,810 | 521,301 | A | G | 1.29 | 10−8 (10−2) * | 32959083 |
7p15.2 | NFE2L3/HOXA10 | rs12700667 | 3194 | 7060 | A | G | 1.22 | 10−7 | 3019124 |
rs12700667 | 2392 | 2271 | A | G | 1.17 | 10−3 | 3019124 ** | ||
rs12700667 | 4604 | 9393 | A | G | 1.18 | 10−10 | 23104006 | ||
rs12700667 | 1044 | 4017 | A | G | NA | 10−9 | 23104006 ** | ||
rs12700667 | 998 | 783 | A | G | 1.19 | 10−10 | 26337243 | ||
rs12700667 | 11,506 | 32,678 | A | G | 1.13 | 10−9 | 24676469 | ||
rs12700667 | 17,045 | 191,596 | A | G | 1.1 | 10−10 | 28537267 | ||
rs12700667 | 315 | 406 | A | G | 1.3 | 10−2 | 30010178 ** | ||
7p22.3 | C7orf50 | rs10256972 | 1448 | 1540 | A | C | 1.30 | 10−6 | 27506219 |
7q31.1 | DNAJB9 | rs11561993 | 187,810 | 521,301 | T | C | 1.025 | 10−9 (10−3) * | 32959083 |
8q24.21 | GSDMC | rs11784932 | 187,810 | 521,301 | A | C | 1.026 | 10−8 (10−4) * | 32959083 |
9p21.1 | THEM215-APTX | rs7042500 | 3194 | 2057 | A | G | 0.9 | 10−5 | 29608257 |
9p21.1 | ACO1 | rs13299293 | 187,810 | 521,301 | A | T | 0.976 | 10−9 (10−3) * | 32959083 |
9p21.3 | CDKN2B-AS1 | rs10965235 | 1907 | 5292 | C | A | 1.44 | 10−12 | 20601957 |
rs1537377 | 11,506 | 32,678 | C | T | 1.12 | 10−8 | 24676469 | ||
rs1537377 | 17,045 | 191,596 | T | C | 1.21 | 10−9 | 28537267 | ||
rs1537377 | 4604 | 9393 | C | T | 1.15 | 10−6 | 23104006 | ||
rs1537377 | 1044 | 4017 | C | T | NA | 10−4 | 23104006 ** | ||
rs1448792 | 17,045 | 191,596 | G | A | 1.08 | 10−8 | 28537267 | ||
rs10757272 | 17,045 | 191,596 | C | T | 1.07 | 10−7 | 28537267 | ||
9p24.1-p23 | PTRD | rs2475335 | 3194 | 2057 | T | C | 1.11 | 10−8 | 29608257 |
9p24.1-p23 | PTPRD | rs1931391 | 187,810 | 521,301 | T | G | 1.031 | 10−8 (10−2) * | 32959083 |
9q33.1 | TRIM32 | rs11793648 | 46,262 | 364,789 | NA | NA | NA | 10−6 | 32121467 |
10p13 | CUBN | rs1801232 | 7164 | 21,005 | T | G | 0.86 | 10−7 | 28900119 |
10q11.21 | HNRNPA3P1 | rs10508881 | 2019 | 14,471 | A | G | 1.19 | 10−7 | 23472165 ** |
10q11.21 | LOC100130539 | ||||||||
10q25.2 | VTI1A | rs2479037 | 288 | 259 | C | T | 4.36 | 10−3 | 25722978 |
11p14.1 | FSHB | rs74485684 | 17,045 | 191,596 | G | A | 1.11 | 10−8 | 28537267 |
rs11031006 | 35,474 | 267,505 | A | G | 1,10 | 10−15 | 31649266 | ||
11p14.1 | ARL14EP | rs4071559 | 46,262 | 364,789 | NA | NA | NA | 10−7 | 32121467 |
11q14.3 | TYR | rs7933594 | 187,810 | 521,301 | C | G | 1.024 | 10−9 (10−2) * | 32959083 |
12p13.32 | PARP11-CCND2 | rs10459129 | 3194 | 2057 | A | G | 0.9 | 10−5 | 29608257 |
12q21.32-12q21.33 | KITLG-DUSP6 | rs12303900 | 3194 | 2057 | G | T | 1.28 | 10−7 | 29608257 |
12q22 | VEZT | rs10859871 | 11,506 | 32,678 | C | A | 1.18 | 10−15 | 24676469 |
rs10859871 | 4604 | 9393 | C | A | 1.20 | 10−9 | 23104006 | ||
rs10859871 | 23,671 | 68,894 | C | A | 1.19 | 10−20 | 27470151 | ||
rs10859871 | 998 | 783 | C | A | 1.16 | 10−7 | 26337243 | ||
rs10859871 | 1044 | 4017 | C | T | NA | 10−6 | 23104006 ** | ||
rs4762326 | 17,045 | 191,596 | T | C | 1.08 | 10−8 | 28537267 | ||
13q21.1 | PCDH17 | rs9538160 | 187,810 | 521,301 | A | G | 0.976 | 10−8 (10−3) * | 32959083 |
13q22.2-13q22.3 | LMO7-KCTD12 | rs9530566 | 3194 | 2057 | C | A | 1.08 | 10−5 | 29608257 |
14q23.2-14q23.2 | PARP1P2/RHOJ | rs10129516 | 171 | 2934 | T | C | 3.01 | 10−10 | 28881265 |
15q26.2 | NR2F2 | rs35625885 | 187,810 | 521,301 | A | G | 0.965 | 10−8 (10−2) * | 32959083 |
15q26.3 | IGF-1R | rs4966038 | 1448 | 1540 | C | G | 1.40 | 10−9 | 27506219 |
17p13.1 | SLC35G6 | rs9891297 | 46,262 | 364,789 | NA | NA | NA | 10−6 | 32121467 |
17q21.32 | SKAP1 | rs2278868 | 3194 | 2057 | C | T | 0.92 | 10−6 | 29608257 |
17q24.1 | CEP112 | rs17693745 | 3194 | 2057 | T | C | 1.08 | 10−5 | 29608257 |
19q12 | ZNF536-TSHZ3 | rs2198894 | 3194 | 2057 | T | C | 1.09 | 10−5 | 29608257 |
20q13.33 | LAMA5 | rs2427284 | 394 | 650 | A | G | 0.49 | 10−3 | 30044155 ** |
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Lalami, I.; Abo, C.; Borghese, B.; Chapron, C.; Vaiman, D. Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing. Int. J. Mol. Sci. 2021, 22, 7297. https://doi.org/10.3390/ijms22147297
Lalami I, Abo C, Borghese B, Chapron C, Vaiman D. Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing. International Journal of Molecular Sciences. 2021; 22(14):7297. https://doi.org/10.3390/ijms22147297
Chicago/Turabian StyleLalami, Imane, Carole Abo, Bruno Borghese, Charles Chapron, and Daniel Vaiman. 2021. "Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing" International Journal of Molecular Sciences 22, no. 14: 7297. https://doi.org/10.3390/ijms22147297