Family studies of schizophrenia and pregnancy outcomes
Author: Svensson, Anna
Date: 2009-01-16
Location: Hillarpsalen, Retzius väg 8
Time: 09.00
Department: Institutionen för medicinsk epidemiologi och biostatistik / Department of Medical Epidemiology and Biostatistics
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Thesis (665.1Kb)
Abstract
Why do psychiatric diseases run in families? Why do some women tend to have similar obstetric complications in subsequent pregnancies? The overall aim of this thesis was to investigate how genes and environments contribute to the aggregation of schizophrenia and adverse pregnancy outcomes in some families. Further, we also studied the fertility in families of patients with schizophrenia. All papers were based on data from the population-based Multi-Generation Register, which has information on familial relationships between Swedish residents.
In Paper I, we explored the fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in patients with schizophrenia is compensated by an increased rate in their first-degree relatives, as suggested by previous studies. We found reduced fertility in patients with schizophrenia as well as among their offspring. In contrast to previous studies we accounted for selection bias of larger families and found that the reduced fertility was not compensated by higher parental or sibling fertility.
In Paper II, we investigated the possible moderating effect of individual characteristics (such as age at onset of disease and season of birth) and parental characteristics (such as paternal age, family history and immigrant status) on familial aggregation of schizophrenia. The familial aggregation, as measured by the sibling recurrence-risk ratios, was reduced by higher age at onset, schizophrenia in parents, advancing paternal age and immigrant status of parents. No interaction between seasonality of birth and familiality of schizophrenia was detected. There was a monotonic decrease in the sibling recurrence-risk ratio with higher age at onset of the proband. However, the familiality remained high across the different levels of the covariates, indicating a high genetic contribution during all conditions.
In Paper III and IV, we studied offspring of siblings to disentangle the genes from the mother, the genes from the child and the environmental effects on the risk of having small for gestational age (SGA) and preterm birth. In Paper IV, we also evaluated if the familial aggregation was explained by exposure to shared risk factors. Preterm birth and SGA seem to have different etiologies. Genetic factors accounted for almost half of the liability to have SGA births and these genetic effects were primarily due to fetal genes. In contrast, fetal genes explained only a small fraction of the total variation in liability to preterm birth. Our results suggest the important role of maternal genes on the risk of preterm birth and these maternal effects are independent of well known risk factors for preterm birth.
In conclusion, by using the unique possibilities in the Swedish populationbased registries, we could show that genetic effects are most important for the familial aggregation for both schizophrenia and in birth complications. Nevertheless, environmental effects were also involved. Thus, the gene environment interplay should be considered when searching for the etiological factors that contribute to schizophrenia and obstetric complications.
In Paper I, we explored the fertility of parents, siblings and offspring to patients with schizophrenia, to test the hypothesis that the decreased reproductive rate in patients with schizophrenia is compensated by an increased rate in their first-degree relatives, as suggested by previous studies. We found reduced fertility in patients with schizophrenia as well as among their offspring. In contrast to previous studies we accounted for selection bias of larger families and found that the reduced fertility was not compensated by higher parental or sibling fertility.
In Paper II, we investigated the possible moderating effect of individual characteristics (such as age at onset of disease and season of birth) and parental characteristics (such as paternal age, family history and immigrant status) on familial aggregation of schizophrenia. The familial aggregation, as measured by the sibling recurrence-risk ratios, was reduced by higher age at onset, schizophrenia in parents, advancing paternal age and immigrant status of parents. No interaction between seasonality of birth and familiality of schizophrenia was detected. There was a monotonic decrease in the sibling recurrence-risk ratio with higher age at onset of the proband. However, the familiality remained high across the different levels of the covariates, indicating a high genetic contribution during all conditions.
In Paper III and IV, we studied offspring of siblings to disentangle the genes from the mother, the genes from the child and the environmental effects on the risk of having small for gestational age (SGA) and preterm birth. In Paper IV, we also evaluated if the familial aggregation was explained by exposure to shared risk factors. Preterm birth and SGA seem to have different etiologies. Genetic factors accounted for almost half of the liability to have SGA births and these genetic effects were primarily due to fetal genes. In contrast, fetal genes explained only a small fraction of the total variation in liability to preterm birth. Our results suggest the important role of maternal genes on the risk of preterm birth and these maternal effects are independent of well known risk factors for preterm birth.
In conclusion, by using the unique possibilities in the Swedish populationbased registries, we could show that genetic effects are most important for the familial aggregation for both schizophrenia and in birth complications. Nevertheless, environmental effects were also involved. Thus, the gene environment interplay should be considered when searching for the etiological factors that contribute to schizophrenia and obstetric complications.
List of papers:
I. Svensson AC, Lichtenstein P, Sandin S, Hultman CM (2007). Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. Schizophr Res. 91(1-3): 238-45. Epub 2007 Jan 31
Pubmed
II. Svensson AC, Lichtenstein P, Sandin S, Öberg S, Sullivan PF, Hultman CM (2008). Familial aggregation of schizophrenia: the moderating effect of age at onset, parental characteristics and season of birth. [Submitted]
III. Svensson AC, Pawitan Y, Cnattingius S, Reilly M, Lichtenstein P (2006). Familial aggregation of small-for-gestational-age births: the importance of fetal genetic effects. Am J Obstet Gynecol. 194(2): 475-9
Pubmed
IV. Svensson AC, Sandin S, Cnattingius S, Reilly M, Pawitan Y, Hultman CM, Lichtenstein P (2008). Maternal effects for preterm birth: common risk factors of importance. [Submitted]
I. Svensson AC, Lichtenstein P, Sandin S, Hultman CM (2007). Fertility of first-degree relatives of patients with schizophrenia: a three generation perspective. Schizophr Res. 91(1-3): 238-45. Epub 2007 Jan 31
Pubmed
II. Svensson AC, Lichtenstein P, Sandin S, Öberg S, Sullivan PF, Hultman CM (2008). Familial aggregation of schizophrenia: the moderating effect of age at onset, parental characteristics and season of birth. [Submitted]
III. Svensson AC, Pawitan Y, Cnattingius S, Reilly M, Lichtenstein P (2006). Familial aggregation of small-for-gestational-age births: the importance of fetal genetic effects. Am J Obstet Gynecol. 194(2): 475-9
Pubmed
IV. Svensson AC, Sandin S, Cnattingius S, Reilly M, Pawitan Y, Hultman CM, Lichtenstein P (2008). Maternal effects for preterm birth: common risk factors of importance. [Submitted]
Issue date: 2008-12-26
Rights:
Publication year: 2009
ISBN: 978-91-7409-278-3
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