Disease Clusters?

Groups of diseases that share a large number of curated genes with each other, computed via label propagation over the shared-gene similarity graph. See also Shared-Gene Disease Pairs for pairwise comparisons.

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Cluster 32

17 diseases · 32 shared-gene connections
17 Diseases
404 Unique genes
0.069 Avg. similarity score
Spermatogenic failure Most-connected disease (10 links)
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Disease Searched: ciliary dyskinesia, primary, 45 Pinned (dragged)
Node size = connections within this cluster · edge thickness = similarity strength · hover an edge for its details · click a node to select it and show its pairs below (double-click or Ctrl/⌘-click opens the disease page) · drag a node to pin it in place · scroll/pinch to zoom.

Member diseases (most connected first ‐ the cluster's core)

Disease ⇵ Connections in cluster ⇵ Significant partners ⇵ Curated genes ⇵
Spermatogenic failure 10 10 114
Congenital impairment of spermatozoa motility 6 6 23
Male infertility single gene azoospermia 6 6 107
Teratozoospermia 6 6 27
Azoospermia 5 5 32
Premature ovarian failure 5 5 114
Testicular azoospermia 5 5 33
Male infertility 4 4 111
SYCE1-related gametogenic failure 3 3 1
Spermatogenic failure, x-linked 3 3 8
spermatogenic failure 38 3 3 1
Male infertility teratozoospermia 2 2 2
Synovial sarcoma 2 2 3
Congenital alpha-fetoprotein deficiency 1 1 1
Ruijs-aalfs syndrome 1 1 1
X-linked intellectual disability, Cabezas type 1 1 1
ciliary dyskinesia, primary, 45 1 1 1

Top shared genes (genes linked to 2+ member diseases ‐ top 100 shown, download for all)

Gene ⇵ Member diseases ⇵ Linked diseases
C14ORF39 5 / 17 Azoospermia, Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure and 1 more
MOV10L1 5 / 17 Azoospermia, Male infertility, Male infertility single gene azoospermia, Spermatogenic failure and 1 more
MSH5 5 / 17 Azoospermia, Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure and 1 more
NR5A1 5 / 17 Male infertility, Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure and 1 more
ARMC2 4 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure, spermatogenic failure 38, Teratozoospermia
DMRT1 4 / 17 Male infertility, Male infertility single gene azoospermia, spermatogenic failure, Testicular azoospermia
DNAH10 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, Teratozoospermia
FANCM 4 / 17 Azoospermia, Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure
GCNA 4 / 17 Azoospermia, Male infertility single gene azoospermia, Spermatogenic failure, x-linked, Testicular azoospermia
M1AP 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
MEIOB 4 / 17 Azoospermia, Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure
PNLDC1 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
SHOC1 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
STAG3 4 / 17 Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure, Testicular azoospermia
SYCE1 4 / 17 Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure, SYCE1-related gametogenic failure
SYCP3 4 / 17 Azoospermia, Male infertility, Male infertility single gene azoospermia, Spermatogenic failure
TDRD9 4 / 17 Azoospermia, Male infertility, Male infertility single gene azoospermia, Spermatogenic failure
TERB1 4 / 17 Azoospermia, Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
TEX11 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, x-linked, Testicular azoospermia
USP26 4 / 17 Congenital impairment of spermatozoa motility, Male infertility, Spermatogenic failure, x-linked, Teratozoospermia
ZMYND15 4 / 17 Male infertility, Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
BRDT 3 / 17 Azoospermia, Premature ovarian failure, Spermatogenic failure
CATSPER1 3 / 17 Congenital impairment of spermatozoa motility, Male infertility, Spermatogenic failure
CFAP251 3 / 17 Congenital impairment of spermatozoa motility, Male infertility teratozoospermia, Spermatogenic failure
CFAP43 3 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure, Teratozoospermia
CFTR 3 / 17 Azoospermia, Male infertility, Male infertility single gene azoospermia
DMC1 3 / 17 Azoospermia, Spermatogenic failure, Testicular azoospermia
DNAH1 3 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure, Teratozoospermia
DNAH6 3 / 17 Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure
FAHD1 3 / 17 Azoospermia, Premature ovarian failure, Spermatogenic failure
KASH5 3 / 17 Azoospermia, Premature ovarian failure, Spermatogenic failure
KLHL10 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
MCM9 3 / 17 Male infertility, Premature ovarian failure, Testicular azoospermia
MSH4 3 / 17 Premature ovarian failure, Spermatogenic failure, Testicular azoospermia
NOS3 3 / 17 Male infertility, Premature ovarian failure, Teratozoospermia
PDHA2 3 / 17 Azoospermia, Male infertility single gene azoospermia, Spermatogenic failure
REC8 3 / 17 Azoospermia, Premature ovarian failure, Testicular azoospermia
RNF212 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
SPAG17 3 / 17 Congenital impairment of spermatozoa motility, Male infertility single gene azoospermia, Spermatogenic failure
SSX1 3 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure, x-linked, Synovial sarcoma
SYCP2 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
TERB2 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
TEX14 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
TEX15 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
TTC21A 3 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure, Teratozoospermia
XRCC2 3 / 17 Male infertility single gene azoospermia, Premature ovarian failure, Spermatogenic failure
ZSWIM7 3 / 17 Male infertility single gene azoospermia, Spermatogenic failure, Testicular azoospermia
ACTL7A 2 / 17 Male infertility, Spermatogenic failure
ACTL9 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
ADCY10 2 / 17 Male infertility, Teratozoospermia
AFP 2 / 17 Congenital alpha-fetoprotein deficiency, Premature ovarian failure
AK7 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
AKAP4 2 / 17 Congenital impairment of spermatozoa motility, Teratozoospermia
AURKC 2 / 17 Male infertility, Spermatogenic failure
AXDND1 2 / 17 Male infertility, Testicular azoospermia
BCL2 2 / 17 Azoospermia, Male infertility
BNC1 2 / 17 Male infertility single gene azoospermia, Premature ovarian failure
BRWD1 2 / 17 Male infertility, Premature ovarian failure
CATIP 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
CATSPER2 2 / 17 Male infertility, Spermatogenic failure
CCDC146 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
CCDC34 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
CFAP44 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
CFAP65 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
CFAP69 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
CFAP70 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
CFAP91 2 / 17 Male infertility teratozoospermia, Spermatogenic failure
CT55 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure, x-linked
CUL4B 2 / 17 Teratozoospermia, X-linked intellectual disability, Cabezas type
CYP17A1 2 / 17 Male infertility, Premature ovarian failure
DCAF6 2 / 17 Male infertility, Teratozoospermia
DDX25 2 / 17 Azoospermia, Male infertility single gene azoospermia
DNAH17 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
DNAH3 2 / 17 Male infertility, Spermatogenic failure
DNHD1 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
DRC1 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
FBXO43 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
FKBP6 2 / 17 Male infertility, Spermatogenic failure
FSIP2 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
HENMT1 2 / 17 Azoospermia, Male infertility
HFM1 2 / 17 Azoospermia, Premature ovarian failure
HORMAD1 2 / 17 Male infertility, Male infertility single gene azoospermia
MCM8 2 / 17 Azoospermia, Premature ovarian failure
MCMDC2 2 / 17 Azoospermia, Male infertility single gene azoospermia
NANOS1 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
NCKAP5 2 / 17 Male infertility, Premature ovarian failure
PIWIL2 2 / 17 Male infertility, Male infertility single gene azoospermia
PMFBP1 2 / 17 Spermatogenic failure, Teratozoospermia
POLG 2 / 17 Male infertility, Premature ovarian failure
RPL10L 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
SEPTIN12 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
SEPTIN4 2 / 17 Male infertility, Spermatogenic failure
SLC26A8 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
SOHLH1 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
SPATA16 2 / 17 Spermatogenic failure, Teratozoospermia
SPATA22 2 / 17 Premature ovarian failure, Spermatogenic failure
SPEF2 2 / 17 Congenital impairment of spermatozoa motility, Spermatogenic failure
SPINK2 2 / 17 Male infertility single gene azoospermia, Spermatogenic failure
SPRTN 2 / 17 Ruijs-aalfs syndrome, Teratozoospermia
STX2 2 / 17 Male infertility, Spermatogenic failure
What do these columns mean?
Connections in cluster
How many other members this disease has a shared-gene link to (the node size in the network above). The most-connected diseases are the cluster's core.
Significant partners
How many of those links are statistically significant (FDR q < 0.05).
Curated genes
Distinct curated genes linked to that disease in GeDiPNet.
Member diseases (Top shared genes)
How many of this cluster's diseases are linked to the gene, out of the cluster's total. Genes shared by many members are the most direct explanation of why they group together.
Overlap genes (x / y)
x = genes shared between this cluster and the pathway/GO term; y = that pathway/GO term's total gene count. A higher x relative to y (and to the cluster's own size) means a tighter biological match.
Cluster gene count
Total distinct genes across every disease in this cluster -- the "n" used in the significance test below.
Fold enrichment
Observed overlap divided by the overlap expected by chance, given the cluster's gene count, the pathway/term's size and the gene universe tested. 5× means five times more shared genes than random. Tells strong hits apart when q-values are all vanishingly small.
P-value / FDR q-value
Is this pathway/GO term's overlap with the cluster more than chance? Upper-tail hypergeometric test, Benjamini-Hochberg corrected across every tested pathway/term (prefer the q-value -- it accounts for testing many at once).
Shared genes (Pairs within this cluster)
Number of curated genes the two diseases in that row have in common.
Similarity score (Pairs within this cluster)
Jaccard-based gene overlap between the two specific diseases in that row -- same metric as the main Shared-Gene Disease Pairs page.

Enriched Pathways (why this cluster is grouped, biologically)

Pathway ⇵ Source ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
Ovarian steroidogenesis
CYP17A1, CYP1A1, FSHB, LHB, LHCGR, BMP15, BMP6, CYP19A1, SCARB1
 KEGG 9 / 52 5.1× 5.14e-5 1.27e-3 ✓ sig.
Prolactin signaling pathway
CYP17A1, ESR1, LHB, LHCGR, ESR2, MAP2K1, SOS1, GALT, JAK2, PRLR
 KEGG 10 / 71 4.2× 1.22e-4 2.57e-3 ✓ sig.
Sperm Motility And Taxes
CATSPER1, CATSPER2, CATSPERB, KCNU1
 Reactome 4 / 9 13.2× 1.39e-4 2.84e-3 ✓ sig.
Hormone ligand-binding receptors
FSHB, GNRH1, LHB, LHCGR
 Reactome 4 / 12 9.9× 5.04e-4 7.91e-3 ✓ sig.
Chronic myeloid leukemia
BAX, CBL, MDM2, TP53, MAP2K1, PTPN11, SOS1, MECOM, MYC
 KEGG 9 / 77 3.5× 1.08e-3 1.42e-2 ✓ sig.
Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
MTR, MTRR
 Reactome 2 / 2 29.7× 1.13e-3 1.47e-2 ✓ sig.
Defective MTR causes methylmalonic aciduria and homocystinuria type cblG
MTR, MTRR
 Reactome 2 / 2 29.7× 1.13e-3 1.47e-2 ✓ sig.
SUMOylation of intracellular receptors
AR, ESR1, NR1H4, NR5A1, NR5A2
 Reactome 5 / 27 5.5× 1.84e-3 2.15e-2 ✓ sig.
Motor proteins
DNAH1, DNAH17, DNAH10, DNAH11, DNAH3, DNAH5, DNAI1, MYO6, DNAH6, DNAH7, TUBB3, DNAH12
 KEGG 15 / 194 2.3× 2.33e-3 2.55e-2 ✓ sig.
GLI proteins bind promoters of Hh responsive genes to promote transcription
GLI2, GLI1
 Reactome 2 / 3 19.8× 3.31e-3 3.29e-2 ✓ sig.
MAPK3 (ERK1) activation
MAP2K1, PTPN11, JAK2
 Reactome 3 / 10 8.9× 3.80e-3 3.62e-2 ✓ sig.
Huntington disease
DNAH1, DNAH17, BAX, SOD2, TP53, DNAH10, DNAH11, DNAH3, DNAH5, DNAI1, DNAH6, DNAH7
 KEGG 20 / 308 1.9× 3.83e-3 3.64e-2 ✓ sig.
Autophagy - other
ATG2A, ATG7, ATG9B, ATG4D, ATG5
 KEGG 5 / 32 4.6× 4.00e-3 3.75e-2 ✓ sig.
Stabilization of p53
MDM2, TP53, CHEK2
 Reactome 3 / 11 8.1× 5.10e-3 4.43e-2 ✓ sig.
Interleukin-6 signaling
CBL, PTPN11, JAK2
 Reactome 3 / 11 8.1× 5.10e-3 4.43e-2 ✓ sig.

Enriched GO Terms (Biological Process, a second line of biological evidence)

GO term ⇵ GO ID ⇵ Overlap genes ⇵ Fold enrichment ⇵ P-value ⇵ FDR q-value ⇵
spermatogenesis
BRDT, DDX25, DMC1, ERCC1, KASH5, MCMDC2, MOV10L1, REC8, TDRD9, TDRKH, AKAP4, ARMC2
 GO:0007283 102 / 556 8.5× 4.88e-66 3.44e-61 ✓ sig.
meiotic cell cycle
BRDT, DMC1, HFM1, KASH5, MCMDC2, MEIOB, MSH5, REC8, SYCP3, TDRD9, TERB1, SLC26A8
 GO:0051321 45 / 137 15.2× 5.64e-41 6.42e-37 ✓ sig.
cell differentiation
BRDT, DDX25, SOX5, TDRD9, TDRKH, ARMC2, CATSPER1, CFAP69, SEPTIN12, SLC26A8, SPAG17, SPEF2
 GO:0030154 88 / 1,051 3.9× 7.01e-29 3.48e-25 ✓ sig.
piRNA processing
HENMT1, MOV10L1, TDRD9, TDRKH, TDRD7, DDX4, FKBP6, GPAT2, MAEL, PIWIL1, PIWIL2, PLD6
 GO:0034587 17 / 21 37.4× 1.95e-25 7.01e-22 ✓ sig.
flagellated sperm motility
AKAP4, ARMC2, CATSPER1, CFAP251, CFAP43, CFAP44, CFAP65, CFAP69, DNAH1, DRC1, FSIP2, TTC21A
 GO:0030317 32 / 142 10.4× 1.13e-23 3.19e-20 ✓ sig.
spermatid development
DDX25, DMC1, REC8, SYCP3, TTC21A, ACTL7A, ADCY10, GALNTL5, PIWIL1, PLD6, SOX30, ZMYND15
 GO:0007286 28 / 120 10.8× 2.68e-21 5.20e-18 ✓ sig.
male meiotic nuclear division
BRDT, MEIOB, TDRD9, TDRKH, DDX4, MAEL, TDRD12, TEX11, ASZ1, SYCP2, TEX14, TEX15
 GO:0007140 15 / 31 22.4× 1.79e-17 1.90e-14 ✓ sig.
fertilization
MEIOB, REC8, TDRD9, TDRKH, ACTL9, AR, BAX, ACTL7A, CATSPER2, KLK14, MAEL, TDRD12
 GO:0009566 18 / 54 15.4× 3.48e-17 3.51e-14 ✓ sig.
homologous chromosome pairing at meiosis
DMC1, KASH5, MEIOB, REC8, TERB1, HORMAD1, MAEL, RNF212, TERB2, TEX15, MND1, MSH4
 GO:0007129 15 / 33 21.0× 5.92e-17 5.85e-14 ✓ sig.
regulatory ncRNA-mediated gene silencing
HENMT1, TDRD9, TDRKH, DROSHA, DDX4, FKBP6, MAEL, PIWIL1, PIWIL2, TDRD1, TDRD12, ASZ1
 GO:0031047 19 / 65 13.5× 7.49e-17 7.28e-14 ✓ sig.
oogenesis
DMC1, ERCC1, KASH5, MCMDC2, KMT2D, NANOS2, HORMAD1, PIWIL2, NANOS1, STRA8, TAF4B, TERB2
 GO:0048477 17 / 53 14.8× 5.59e-16 4.64e-13 ✓ sig.
cilium movement
CFAP251, CFAP43, CFAP70, TTC29, DNAAF4, CCDC40, DNAH11, DNAH3, DNAH5, DNAI1, ODAD2, DNAH7
 GO:0003341 16 / 48 15.4× 2.03e-15 1.50e-12 ✓ sig.
sperm axoneme assembly
ARMC2, CFAP43, CFAP44, CFAP65, CFAP69, DNAH1, FSIP2, SPEF2, CCDC146, CEP131, CFAP58, TTC12
 GO:0007288 13 / 31 19.4× 2.70e-14 1.63e-11 ✓ sig.
synaptonemal complex assembly
MCMDC2, REC8, HORMAD1, SHOC1, TEX11, STAG3, SYCE1, SYCP2, TERB2, TEX15, MLH3, SPO11
 GO:0007130 12 / 25 22.2× 3.58e-14 2.14e-11 ✓ sig.
reciprocal meiotic recombination
DMC1, HFM1, REC8, SHOC1, TEX11, RNF212, MLH3, MND1, MSH4, RAD51B, RAD51C, RAD54L
 GO:0007131 13 / 33 18.2× 7.21e-14 4.09e-11 ✓ sig.

Pairs within this cluster, by significance

Disease A ⇵ Disease B ⇵ Similarity score ⇵ Shared genes ⇵ P-value ⇵ FDR q-value ⇵
Male infertility single gene azoospermia Spermatogenic failure 0.207 38 1.04e-55 5.93e-54 ✓ sig.
Congenital impairment of spermatozoa motility Spermatogenic failure 0.169 20 7.34e-41 3.13e-39 ✓ sig.
Male infertility single gene azoospermia Testicular azoospermia 0.165 20 5.61e-36 2.11e-34 ✓ sig.
Spermatogenic failure Testicular azoospermia 0.156 20 2.24e-35 8.16e-34 ✓ sig.
Azoospermia Male infertility single gene azoospermia 0.102 13 1.29e-20 2.54e-19 ✓ sig.
Azoospermia Spermatogenic failure 0.097 13 3.07e-20 5.92e-19 ✓ sig.
Male infertility Spermatogenic failure 0.087 18 1.50e-19 2.77e-18 ✓ sig.
Azoospermia Premature ovarian failure 0.073 10 1.86e-14 2.55e-13 ✓ sig.
Male infertility Testicular azoospermia 0.074 10 2.02e-14 2.76e-13 ✓ sig.
Male infertility Male infertility single gene azoospermia 0.068 14 3.07e-14 4.13e-13 ✓ sig.
Premature ovarian failure Spermatogenic failure 0.065 14 1.11e-13 1.42e-12 ✓ sig.
Azoospermia Testicular azoospermia 0.119 7 3.41e-13 4.30e-12 ✓ sig.
Congenital impairment of spermatozoa motility Teratozoospermia 0.133 6 1.58e-12 1.89e-11 ✓ sig.
Male infertility single gene azoospermia Premature ovarian failure 0.052 11 3.83e-10 3.61e-9 ✓ sig.
Spermatogenic failure Teratozoospermia 0.052 7 7.95e-10 7.26e-9 ✓ sig.
Azoospermia Male infertility 0.043 6 9.53e-8 6.68e-7 ✓ sig.
Congenital impairment of spermatozoa motility Spermatogenic failure, x-linked 0.067 2 5.94e-5 2.33e-4 ✓ sig.
Male infertility teratozoospermia Spermatogenic failure 0.017 2 5.43e-5 2.33e-4 ✓ sig.
Spermatogenic failure, x-linked Testicular azoospermia 0.050 2 1.24e-4 3.93e-4 ✓ sig.
Congenital impairment of spermatozoa motility spermatogenic failure 38 0.042 1 1.49e-3 2.31e-3 ✓ sig.
Spermatogenic failure, x-linked Synovial sarcoma 0.091 1 1.56e-3 2.38e-3 ✓ sig.
Teratozoospermia X-linked intellectual disability, Cabezas type 0.036 1 1.75e-3 2.61e-3 ✓ sig.
spermatogenic failure 38 Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Ruijs-aalfs syndrome Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
ciliary dyskinesia, primary, 45 Teratozoospermia 0.036 1 1.75e-3 2.61e-3 ✓ sig.
Congenital impairment of spermatozoa motility Male infertility teratozoospermia 0.040 1 2.99e-3 3.95e-3 ✓ sig.
Congenital impairment of spermatozoa motility Synovial sarcoma 0.038 1 4.47e-3 5.60e-3 ✓ sig.
Male infertility single gene azoospermia SYCE1-related gametogenic failure 0.009 1 6.95e-3 8.23e-3 ✓ sig.
Spermatogenic failure spermatogenic failure 38 0.009 1 7.40e-3 8.70e-3 ✓ sig.
Premature ovarian failure SYCE1-related gametogenic failure 0.009 1 7.40e-3 8.70e-3 ✓ sig.
Spermatogenic failure SYCE1-related gametogenic failure 0.009 1 7.40e-3 8.70e-3 ✓ sig.
Congenital alpha-fetoprotein deficiency Premature ovarian failure 0.009 1 7.40e-3 8.70e-3 ✓ sig.