The heritability of endometriosis
Q2 Rama Saha, M.D.,
a
Hans J€ arnbert Pettersson, Ph.D.,
a
Pia Svedberg, Ph.D.,
b
Matts Olovsson, Ph.D.,
c
Agneta Bergqvist, Ph.D.,
d
Lena Marions, Ph.D.,
a
Per Tornvall, Ph.D.,
a
and Ralf Kuja-Halkola, Ph.D.
e
a
Department of Clinical Science and Education, and
b
Division of Insurance Medicine, Department of Clinical Neurosciences,
Karolinska Institutet, Stockholm, Sweden;
c
Department of Women’s and Children’s Health, Uppsala University, Uppsala,
Sweden;
d
Karolinska Institutet, Stockholm, Sweden; and
e
Department of Medical Epidemiology and Biostatistics,
Karolinska Institutet, Stockholm, Sweden
Objective: To estimate the relative contribution of genetic influences and prevalence on endometriosis.
Design: Analysis of self-reported data from a nationwide population-based twin registry.
Setting: Not applicable.
Patient(s): In total 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who participated in either of two surveys (1998–
2002 or 2005–2006).
Intervention(s): None.
Main Outcome Measure(s): Self-reported endometriosis, validated by medical records.
Result(s): A history of endometriosis was reported by 1,228 female twins. The probandwise concordance was 0.21 for MZ and 0.10 for
DZ twins. Higher within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with DZ (0.20) twins. The best-fitting
model revealed a contribution of 47% by additive genetic factors and the remaining 53% attributed to unique environmental effects.
Conclusion(s): Our findings suggest both genetic and unique (nonshared) environmental influ-
ences on the complex etiology of endometriosis and support the hypothesis that genes have a
strong influence on phenotypic manifestations of endometriosis. (Fertil Steril
Ò
2015;-:
-–-. Ó2015 by American Society for Reproductive Medicine.)
Key Words: Concordance, endometriosis, heritability, twins
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E
ndometriosis is one of the most
common benign gynecologic dis-
eases and is characterized by the
presence of ectopic endometrial tissue
outside the uterus (1). Most estimates of
prevalence have been made on the basis
of surgical populations or small samples
and are therefore highly selective. These
estimates range between 2% and 10% in
women of reproductive age, and the pro-
portion can be up to 50% among infertile
women (2–4). Although the etiology and
pathogenesis of endometriosis remain
largely unknown, there is mounting
evidence that it is a complex
multifactorial disease with both genetic
and environmental components
contributing to susceptibility (4).
Studies on heritability—the presence
of variance accounted for by genetic fac-
tors—have demonstrated familial accu-
mulation (5–7), increased concordance
in monozygotic (MZ) twins (4), and a 3
to 15 times higher risk in first-degree rel-
atives of women with endometriosis
compared with those in the general pop-
ulation (8–11). In an Australian
twin-based study, a twofold increase in
endometriosis risk in MZ compared
with dizygotic (DZ) twin pairs was re-
ported (4), which supports that the
genetic component contributing to
phenotypic variability in endometriosis
is about 50% (4, 12). These and other
findings on heritability have served
as a platform for identification
of susceptibility loci and also
identification of potential candidate
genes using a genomewide association
study strategy in populations of
European descent (13, 14) and in
Japanese populations (15, 16). One
study showed that heritability is also
apparent in nonhuman primates (17).
These data imply that endometriosis
is a complex genetic trait and
indicate that a number of genes
interact with each other to form
disease susceptibility, with the
phenotype emerging in the presence of
environmental risk factors. However,
Received April 22, 2015; revised June 9, 2015; accepted June 27, 2015.
R.S. has nothing to disclose. H.J.P. has nothing to disclose. P.S. has nothing to disclose. M.O. has
nothing to disclose. A.B. has nothing to disclose. L.M. has nothing to disclose. P.T. has nothing
to disclose. R.K.-H. has nothing to disclose.
Supported by the Karolinska Institutet (KI) Research Foundations; grants from the KI Centre for Health
Care Science and the KI Strategic Research Program in Epidemiology (Dnr 7340/2012, to P.S.). The
Swedish Twin Registry is supported by the Department of Higher Education, the Swedish
Research Council, and AstraZeneca, and STAGE was supported by the U.S. National Institutes
of Health [grants DK066134 and CA085739]. The funding sources had no involvement in this
study.
Reprint requests: Rama Saha, M.D., Department of Clinical Science and Education, Karolinska Institu-
tet, S€ odersjukhuset, Sjukhusbacken 10, 118 83 Stockholm, Sweden (E-mail: rama.saha@ki.se).
Fertility and Sterility® Vol. -, No. -, - 2015 0015-0282/$36.00
Copyright ©2015 American Society for Reproductive Medicine, Published by Elsevier Inc.
http://dx.doi.org/10.1016/j.fertnstert.2015.06.035
VOL. - NO. - / - 2015 1
ORIGINAL ARTICLE: ENDOMETRIOSIS
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