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

ArticleinPsychological Medicine 42(7):1515-21 · November 2011with3 Reads
DOI: 10.1017/S0033291711002376 · Source: PubMed
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.
    • "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. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: 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. Methods: A case-control design was applied. A total of 846 cases with schizophrenia were selected from the Danish Psychiatric Case Register. One control was selected for each case, matched on sex and exact date of birth. Results: Both early and late blood sampling was associated with increased risk for schizophrenia. Compared to blood sampling at day 5, sampling at days 0 to 4 after birth was associated with an incidence rate ratio (IRR) of 1.46 (95% CI 1.15-1.87) for development of schizophrenia, and sampling at days 6 to 9 and at days 10 to 53 was associated with an IRR of 1.5 (95% CI 1.13-1.98) and 3.00 (95% CI 1.59-5.67), respectively. After adjusting the estimates for place of birth, both parents' psychiatric illness, maternal and paternal age, parents' country of origin, child admission, and parental education and income, the estimates were slightly different. Thus, blood collection at 0-4days was associated with an IRR of 1.27 (95% CI 0.94-1.71), 6-9days 1.31 (95% CI 0.94-1.84) and 10+days 3.52 (95% CI 1.50 to 8.24). Discussion: After adjusting risk estimates for well-known risk factors, delay in sampling of blood for neonatal screening was associated with unexplained increased risk of schizophrenia. Thus, a key finding is that age at test is a proxy for unobserved risk factors for schizophrenia due to unexplained reasons for late blood sampling. Date of sampling will be included in future analyses of genetic and environmental risk factors.
    Full-text · Article · Jan 2015
    • "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. "
    [Show abstract] [Hide abstract] ABSTRACT: Dried blood spot samples (DBSS) have been collected and stored for decades as part of newborn screening programmes worldwide. Representing almost an entire population under a certain age and collected with virtually no bias, the Newborn Screening Biobanks are of immense value in medical studies, for example, to examine the genetics of various disorders. We have previously demonstrated that DNA extracted from a fraction (2 × 3.2 mm discs) of an archived DBSS can be whole genome amplified (wgaDNA) and used for accurate array genotyping. However, until now, it has been uncertain whether wgaDNA from DBSS can be used for accurate whole genome sequencing (WGS) and exome sequencing (WES).
    Full-text · Article · Jun 2013
  • [Show abstract] [Hide abstract] 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.
    Article · Feb 2013
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