Most previous genome-wide association studies (GWAS) of depression have used data from individuals of European descent. This limits the understanding of the underlying biology of depression and raises questions about the transferability of findings between populations.
The Integrative Psychiatric Research (iPSYCH) consortium has established a large Danish population-based Case-Cohort sample (iPSYCH2012) aimed at unravelling the genetic and environmental architecture of severe mental disorders. The iPSYCH2012 sample is nested within the entire Danish population born between 1981 and 2005, including 1 472 762 persons. This paper introduces the iPSYCH2012 sample and outlines key future research directions. Cases were identified as persons with schizophrenia (N=3540), autism (N=16 146), attention-deficit/hyperactivity disorder (N=18 726) and affective disorder (N=26 380), of which 1928 had bipolar affective disorder. Controls were randomly sampled individuals (N=30 000). Within the sample of 86 189 individuals, a total of 57 377 individuals had at least one major mental disorder. DNA was extracted from the neonatal dried blood spot samples obtained from the Danish Neonatal Screening Biobank and genotyped using the Illumina PsychChip. Genotyping was successful for 90% of the sample. The assessments of exome sequencing, methylation profiling, metabolome profiling, vitamin-D, inflammatory and neurotrophic factors are in progress. For each individual, the iPSYCH2012 sample also includes longitudinal information on health, prescribed medicine, social and socioeconomic information, and analogous information among relatives. To the best of our knowledge, the iPSYCH2012 sample is the largest and most comprehensive data source for the combined study of genetic and environmental aetiologies of severe mental disorders.
Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth.Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth.There were 58 626 (4.34%) preterm births (<37 weeks), 11 732 (0.87%) very preterm births and 3288 (0.24%) extremely preterm births in the study cohort. Severe life events in close relatives in the 6 months before conception increased the risk of preterm birth by 16% (relative risk, RR = 1.16, [95% CI: 1.08-1.23]). Severe life events in older children in the 6 months before conception increased the risk of preterm birth by 23% (RR = 1.23, [95% CI: 1.02-1.49]) and the risk of very preterm birth by 59% (RR = 1.59, [95% CI: 1.08-2.35]).Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth.
Article AbstractObjective: Although rare in absolute terms, risk of homicide is markedly elevated among children of parents with mental disorders. Our aims were to examine risk of child homicide if 1 or both parents had a psychiatric history, to compare effects by parental sex and diagnostic group, and to assess likelihood of child homicide being perpetrated by parents according to their psychiatric history.Method: A prospective, register-based cohort study using the entire Danish population born between January 1, 1973, and January 1, 2007, was conducted. Follow-up of the cohort members began on their date of birth and ended on January 1, 2007; their 18th birthday; their date of death; or their date of emigration, whichever came first. We used the Danish national registers from 1973 to 2007 to study homicide risk between children whose parents were previously admitted to a psychiatric hospital, including diagnosis-specific analyses, versus their unexposed counterparts. In addition, we used police records during 2000 to 2005 to examine whether or not 1 of the parents was the perpetrator. Rates of homicide were analyzed using survival analysis.Results: Children of parents previously admitted to a psychiatric hospital had an overall higher risk of being homicide victims (MRR = 8.94; 95% CI, 6.56-12.18). The risk differed according to parental sex and psychiatric diagnosis (ICD-8 and ICD-10 criteria). The absolute risk of homicide was 0.009% if neither parent had been admitted before the birth of their child and 0.051% if 1 of the parents had previously been admitted. During 2000 to 2005, 88% of the child homicide cases were filicide victims. This percentage was not significantly different for parents with a previous psychiatric admission versus those without such a history.Conclusions: In the large majority of Danish child-homicide cases, a parent was the perpetrator, regardless of whether there had been parental admission to a psychiatric hospital. Children of parents previously admitted had a higher risk of being homicide victims, and risks were especially high in young children whose mothers were hospitalized with affective disorders or schizophrenia. However, the relative risks presented in the current study are based on extremely rare events, and the overwhelming majority of children whose parents have a psychiatric history do not become homicide victims.J Clin PsychiatrySubmitted: July 7, 2009; accepted November 24, 2009.Online ahead of print: October 5, 2010 (doi:10.4088/JCP.09m05508gre).Corresponding author: T. M. Laursen, PhD, Centre for Register-Based Research, Aarhus University, Taasingegade 1, Aarhus, Denmark 8000 (tml@ncrr.dk).
Abstract Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a significant proportion of common risk variation. Understanding the genetic factors underlying the specific symptoms of these disorders will be crucial for improving diagnosis, intervention and treatment. In case-control data consisting of 53,555 cases (20,129 BD, 33,426 SCZ) and 54,065 controls, we identified 114 genome-wide significant loci (GWS) when comparing all cases to controls, of which 41 represented novel findings. Two genome-wide significant loci were identified when comparing SCZ to BD and a third was found when directly incorporating functional information. Regional joint association identified a genomic region of overlapping association in BD and SCZ with disease-independent causal variants indicating a fourth region contributing to differences between these disorders. Regional SNP-heritability analyses demonstrated that the estimated heritability of BD based on the SCZ GWS regions was significantly higher than that based on the average genomic region (91 regions, p = 1.2×10 −6 ) while the inverse was not significant (19 regions, p=0.89). Using our BD and SCZ GWAS we calculated polygenic risk scores and identified several significant correlations with: 1) SCZ subphenotypes: negative symptoms (SCZ, p=3.6×10 −6 ) and manic symptoms (BD, p=2×10 −5 ), 2) BD subphenotypes: psychotic features (SCZ p=1.2×10 −10 , BD p=5.3×10 −5 ) and age of onset (SCZ p=7.9×10 −4 ). Finally, we show that psychotic features in BD has significant SNP-heritability (h 2 snp =0.15, SE=0.06), and a significant genetic correlation with SCZ (r g =0.34) in addition there is a significant sign test result between SCZ GWAS and a GWAS of BD cases contrasting those with and without psychotic features (p=0.0038, one-side binomial test). For the first time, we have identified specific loci pointing to a potential role of 4 genes ( DARS2 , ARFGEF2 , DCAKD and GATAD2A ) that distinguish between BD and SCZ, providing an opportunity to understand the biology contributing to clinical differences of these disorders. Our results provide the best evidence so far of genomic components distinguishing between BD and SCZ that contribute directly to specific symptom dimensions.
Article Abstract Objective: In light of the consistent reduction in suicide rate during the past 20 years in Denmark, this study aims to investigate trends in suicide risk associated with hospitalized psychiatric illness and to explore differences in the changes with regard to clinical phases of illness, sex, age, and diagnosis. Method: This population-based study includes all of 21,169 suicides in Denmark during the years 1981 through 1997 and 423,128 controls matched for sex, age, and time (using a nested case-control design). Personal data on psychiatric history and socioeconomic status were retrieved from Danish longitudinal registers. Data were analyzed using conditional logistic regression. Results: This study shows that the reduction in suicide rate is generally faster among individuals with a history of psychiatric admission than among individuals without such a history. However, this substantial reduction is mainly accounted for by the reduction among patients who had been discharged from psychiatric hospitals for more than 1 year. For patients who had been discharged from hospitals within 1 year, the reduction is similar to that of the general population; while for patients hospitalized for treatment at the time of suicide or the index date, the reduction in suicide rate is relatively slower. Such trends hold for all diagnostic groups. Further analyses stratified by age indicate that the faster reduction in suicide rate associated with history of hospitalized psychiatric illness is more pronounced among patients aged 36 years and older. Conclusion: The reduction in suicide rate is substantial for patients who have been discharged from psychiatric hospitals for more than 1 year and for middle-aged and older patients. Recent improvement in psychiatric care and treatment and promotion of new generation antidepressants may contribute to these changes.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)