Article

Risk of schizophrenia in relation to parental origin and genome-wide divergence

National Centre for Register-based-Research, Aarhus University, Aarhus, Denmark.
Psychological Medicine (Impact Factor: 5.43). 11/2011; 42(7):1515-21. DOI: 10.1017/S0033291711002376
Source: PubMed

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.

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    • "For each case, we randomly selected one control based on the following matching criteria: (a) sex; (b) exact date of birth; (c) born in Denmark; (d) alive and with no history of schizophrenia on the date of first diagnosis of schizophrenia of the matched case. The sample is identical to that described previously (Pedersen et al., 2012). Case–control pairs without exact date for the neonatal screening were excluded. "
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    • "The excess DBSS material from the Danish Newborn Screening programme has been stored in the DNSB [5] since 1982 and covers close to 100% of the Danish population born since that time. Combined with data from numerous Danish registries, the DBSS has been used successfully in several genetic studies of disease looking at cerebral palsy [9], schizophrenia [10] [11] [12] [13] [14] [15] [16], birth weight [17], psychosis [18] [19], and infantile hypertrophic pyloric stenosis [20]. In many countries and states, the neonatal screening programmes are storing the excess DBSS in biobanks, if allowed by law. "
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    ABSTRACT: IMPORTANCE Although increased risk for schizophrenia among immigrants is well established, knowledge of the broader spectrum of psychiatric disorders associated with a foreign migration background is lacking. OBJECTIVE To examine the full range of psychiatric disorders associated with any type of foreign migration background among persons residing in Denmark, including foreign-born adoptees, first- and second-generation immigrants, native Danes with a history of foreign residence, and persons born abroad to Danish expatriates. DESIGN AND SETTING Danish population-based cohort study. Persons were followed up from their 10th birthday for the development of mental disorders based on outpatient and inpatient data. PARTICIPANTS All persons born between January 1, 1971, and December 31, 2000 (N = 1 859 419) residing in Denmark by their 10th birthday with follow-up data to December 31, 2010. MAIN OUTCOME MEASURES Incidence rate ratios (IRRs) and cumulative incidences for psychiatric outcomes. RESULTS All categories of foreign migration background, except persons born abroad to Danish expatriates, were associated with increased risk for at least 1 psychiatric disorder. Foreign-born adoptees had increased IRRs for all psychiatric disorders and had the highest IRRs for these disorders compared with other foreign migration categories. First- and second-generation immigrants having 2 foreign-born parents had significantly increased IRRs for schizophrenia and schizophrenia spectrum disorders and had similar risk magnitudes. Second-generation immigrants having 1 foreign-born parent had significantly increased IRRs for all psychiatric disorders. Native Danes with a history of foreign residence had increased IRRs for bipolar affective disorder, affective disorders, personality disorders, and schizophrenia spectrum disorders. CONCLUSIONS AND RELEVANCE The extent to which a background of foreign migration confers an increased risk for the broad spectrum of psychiatric disorders varies according to parental origin, with greatest risks for foreign-born adoptees. The spectrum of psychiatric disorders showed greater variation within the second-generation immigrant group than between first-generation vs second-generation immigrants, and the spectrum differed according to whether individuals had 1 or 2 foreign-born parents.
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