374 Current understanding of the cause of preeclampsia and eclampsia of pregnancy is limited, although specific aspects of the pathogenesis are understood 1 and precon- ceptional and pregnancy-associated risk factors have been identified. 2 Genetic influences have long been re- garded as etiologically important in preeclampsia and eclampsia, 3 and although several candidates have been identified for preeclampsia 4 and pregnancy-induced hy- pertension, 5 predisposing genes have yet to be indis- putably found. A family history of preeclampsia or eclampsia is associated with a 4-fold increase in the rela- tive risk of severe preeclampsia in primigravid women. 6 After a prolonged period of questioning the (maternal) genetic basis of preeclampsia and eclampsia because no concordant monozygotic twin pairs had been described, 3 monozygotic female twin pairs concordant for pre- eclampsia have now been reported. 7 No twin pair con- cordance and discordance rates were available from that study, however, so no conclusions were possible concern- ing maternal genetic influences. A recent British study reported negligible heritability of confirmed proteinuric preeclampsia, on the basis of data from a cohort of adult female twin pairs. 8 Whether the genetic origin of pre- eclampsia and eclampsia is fetal rather than stemming from the maternal genotype alone or is the result of an interaction between the two is still unresolved. 9 Implan- tation failure is a key feature of preeclampsia and eclampsia. 10 Pairs of monozygotic twins share the same genotype and, if raised in the same family, share the same family background. Dizygotic twins share, on average, 50% of their genes. Differences between monozygotic twins in a pair must be caused by either environmental influences or measurement error, whereas differences between di- zygotic twins may be caused by effects of differing genetic or individual-specific environmental effects. We describe an exploratory epidemiologic study that sought to iden- tify concordance and discordance rates for a history of preeclampsia or eclampsia in pregnancies of adult twin pairs. To investigate a fetal versus a maternal cause of pre- eclampsia and eclampsia, we explored concordance be- tween parous female partners of monozygotic and di- zygotic male co-twins and between female partners and female co-twins in dizygotic opposite-sex pairs. If paternal From the Queensland Institute of Medical Research and the Joint Genet- ics Program, The University of Queensland, Brisbane a ; the School of Bi- ological Sciences, Macquarie University, Sydney b ; the Department of Perinatal Medicine, Royal Women’s Hospital, Melbourne c ; and the De- partment of Obstetrics and Gynaecology, University of Melbourne and Royal Women’s Hospital. d Supported by the Australian National Health and Medical Research Council (grant No. 960744). Received for publication December 9, 1999; revised June 6, 2000; accepted June 12, 2000. Reprint requests: Susan A. Treloar, PhD, Queensland Institute of Med- ical Research, PO Royal Brisbane Hospital, Queensland 4029, Aus- tralia. Copyright © 2001 by Mosby, Inc. 0002-9378/2001 $35.00 + 0 6/1/109400 doi:10.1067/mob.2001.109400 An Australian twin study of the genetic basis of preeclampsia and eclampsia Susan A. Treloar, PhD, a Desmond W. Cooper, PhD, b Shaun P. Brennecke, MB, BS, DPhil, c, d Madonna M. Grehan, RN, RM, c and Nicholas G. Martin, PhD a Brisbane, Queensland, Sydney, New South Wales, and Melbourne, Victoria, Australia OBJECTIVE: We investigated maternal versus fetal genetic causes of preeclampsia and eclampsia by as- sessing concordance between monozygotic and dizygotic female co-twins, between female partners of male monozygotic and dizygotic twin pairs, and between female twins and partners of their male co-twins in di- zygotic opposite-sex pairs. STUDY DESIGN: Two large birth cohorts of volunteer Australian female twin pairs (N = 1504 pairs and N = 858 pairs) were screened and interviewed, and available medical and hospital records were obtained and re- viewed where indicated, with diagnoses assigned according to predetermined criteria. RESULTS: With strict diagnostic criteria used for preeclampsia and eclampsia, no concordant female twin pairs were found. Collapsing diagnoses of definite, probable, or possible preeclampsia or eclampsia resulted in very low genetic recurrence risk estimates. CONCLUSION: Results from these two cohorts of female twin pairs do not support clear, solely maternal ge- netic influences on preeclampsia and eclampsia. Numbers of parous female partners of male twins were too low for conclusions to be drawn regarding paternal transmission. (Am J Obstet Gynecol 2001;184:374-81.) Key words: Genetic, preeclampsia, twin study