Risk of schizophrenia in relation to parental origin and genome-wide divergence
ABSTRACT Second-generation immigrants have an increased risk of schizophrenia, a finding that still lacks a satisfactory explanation. Various operational definitions of second-generation immigrants have been used, including foreign parental country of birth. However, with increasing global migration, it is not clear that parental country of birth necessarily is informative with regard to ethnicity. We compare two independently collected measures of parental foreign ethnicity, parental foreign country of birth versus genetic divergence, based on genome-wide genotypic data, to access which measure most efficiently captures the increased risk of schizophrenia among second-generation immigrants residing in Denmark.
A case-control study covering all children born in Denmark since 1981 included 892 cases of schizophrenia and 883 matched controls. Genetic divergence was assessed using principal component analyses of the genotypic data. Independently, parental foreign country of birth was assessed using information recorded prospectively in the Danish Civil Registration System. We compared incidence rate ratios of schizophrenia associated with these two independently collected measures of parental foreign ethnicity.
People with foreign-born parents had a significantly increased risk of schizophrenia [relative risk (RR) 1.94 (95% confidence intervals (CI) 1.41-2.65)]. Genetically divergent persons also had a significant increased risk [RR 2.43 (95% CI 1.55-3.82)]. Mutual adjustment of parental foreign country of birth and genetic divergence showed no difference between these measures with regard to their potential impact on the results.
In terms of RR of schizophrenia, genetic divergence and parental foreign country of birth are interchangeable entities, and both entities have validity with regard to identifying second-generation immigrants.
SourceAvailable from: Merete Nordentoft[Show abstract] [Hide abstract]
ABSTRACT: The Danish Neonatal Screening Biobank, containing dried blood spot samples from all newborn in Denmark, is a unique source of data that can be utilized for analyses of genetic and environmental exposures related to schizophrenia and other mental disorders. In previous analyses, we have found that early and late blood sampling, compared to sampling at day 5, was associated with increased risk of schizophrenia. As delay in sampling of blood for neonatal screening cannot in itself influence the risk of schizophrenia, it must be seen as a proxy for unknown underlying causes responsible for this association. Therefore, we investigated whether the increased risk can be explained by other risk factors for schizophrenia.Schizophrenia Research 01/2015; 162(1-3). DOI:10.1016/j.schres.2015.01.001 · 4.43 Impact Factor
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ABSTRACT: Introduction: Childhood adversity is gaining increasing attention as a plausible etiological factor in the development of psychotic disorders. Childhood residential mobility is a potential risk factor that has received little attention in this context. Methods: We used registry data to estimate associations of residential mobility with narrow and broad schizophrenia and bipolar disorder across the course of childhood among 1.1 million individuals born in Denmark 1971-1991 and followed from age 15 through 2010. We assessed effect modification by sex, family history of mental disorder, the presence of siblings close in age, and distance moved. Results: In individual-year models adjusted for family history, urbanicity at birth, and parental age, mobility at all ages except the year of birth was associated with heightened risk of narrow and broad schizophrenia, and risk increased with age at moving and with the number of moves. Further adjustment for mobility at all ages 0-15 revealed associations mainly during the latter half of childhood, which were strongest during adolescence. Associations between mobility and bipolar disorder were fewer and weaker compared to schizophrenia. There was modest evidence of interaction with family history of psychiatric diagnosis, but little evidence for interaction by sex, the presence of closely-aged siblings, or distance moved. Schizophrenia associations did not appear attributable to increased mobility among adolescents with earlier onset. Conclusions: Mobility may increase risk for psychotic disorders, particularly schizophrenia. Children may be especially vulnerable during adolescence. Future research should investigate the importance of school changes and the potential for interaction with genetic risk.Schizophrenia Bulletin 06/2014; DOI:10.1093/schbul/sbu074 · 8.61 Impact Factor
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ABSTRACT: IMPORTANCE Understanding the epidemiologic profile of the life course of mental disorders is fundamental for research and planning for health care. Although previous studies have used population surveys, informative and complementary estimates can be derived from population-based registers. OBJECTIVE To derive comprehensive and precise estimates of the incidence rate of and lifetime risk for any mental disorder and a range of specific mental disorders. DESIGN, SETTING, AND PARTICIPANTS We conducted a follow-up study of all Danish residents (5.6 million persons), to whom all treatment is provided by the government health care system without charge to the patient, from January 1, 2000, through December 31, 2012 (total follow-up, 59.5 million person-years). During the study period, 320 543 persons received first lifetime treatment in a psychiatric setting for any mental disorder; 489 006 persons were censored owing to death; and 69 987 persons were censored owing to emigration. Specific categories of mental disorders investigated included organic mental disorders, substance abuse disorders, schizophrenia, mood disorders, anxiety, eating disorders, personality disorders, mental retardation, pervasive developmental disorders, and behavioral and emotional disorders. EXPOSURES Age and sex. MAIN OUTCOMES AND MEASURES Sex- and age-specific incidence rates and cumulative incidences and sex-specific lifetime risks. RESULTS During the course of life, 37.66% of females (95% CI, 37.52%-37.80%) and 32.05% of males (31.91%-32.19%) received their first treatment in a psychiatric setting for any mental disorder. The occurrence of mental disorders varied markedly between diagnostic categories and by sex and age. The sex- and age-specific incidence rates for many mental disorders had a single peak incidence rate during the second and third decades of life. Some disorders had a second peak in the sex- and age-specific incidence rate later in life. CONCLUSIONS AND RELEVANCE This nationwide study provides a first comprehensive assessment of the lifetime risks for treated mental disorders. Approximately one-third of the Danish population received treatment for mental disorders. The distinct signatures of the different mental disorders with respect to sex and age have important implications for service planning and etiologic research.JAMA Psychiatry 05/2014; 71(5):573-81. DOI:10.1001/jamapsychiatry.2014.16 · 12.01 Impact Factor