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Interaction of early environment, gender and genes of monoamine neurotransmission in the aetiology of depression in a large population-based Finnish birth cohort.

ABSTRACT: Objectives Depression is a worldwide leading cause of morbidity and disability. Genetic studies have recently begun to elucidate its molecular aetiology. The authors investigated candidate genes of monoamine neurotransmission and early environmental risk factors for depressiveness in the genetically isolated population-based Northern Finland Birth Cohort 1966 (12?058 live births). Design The authors ascertained and subdivided the study sample (n=5225) based on measures of early development and of social environment, and examined candidate genes of monoamine neurotransmission, many of which have shown prior evidence of a gene-environment interaction for affective disorders, namely SLC6A4, TPH2, COMT, MAOA and the dopamine receptor genes DRD1-DRD5. Results and conclusion The authors observed no major genetic effects of the analysed variants on depressiveness. However, when measures of early development and of social environment were considered, some evidence of interaction was observed. Allelic variants of COMT interacted with high early developmental risk (p=0.005 for rs2239393 and p=0.02 for rs4680) so that the association with depression was detected only in individuals at high developmental risk group (p=0.0046 and ?=0.056 for rs5993883-rs2239393-rs4680 risk haplotype CGG including Val158), particularly in males (p=0.0053 and ?=0.083 for the haplotype CGG). Rs4274224 from DRD2 interacted with gender (p=0.017) showing a significant association with depressiveness in males (p=0.0006 and ?=0.0023; p=0.00005 and ?=0.069 for rs4648318-rs4274224 haplotype GG). The results support the role of genes of monoamine neurotransmission in the aetiology of depression conditional on environmental risk and sex, but not direct major effects of monoaminergic genes in this unselected population.

SUBMITTER: Nyman ES

PROVIDER: S-EPMC3191433 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Interaction of early environment, gender and genes of monoamine neurotransmission in the aetiology of depression in a large population-based Finnish birth cohort.

Nyman Emma S ES Sulkava Sonja S Soronen Pia P Miettunen Jouko J Loukola Anu A Leppä Virpi V Joukamaa Matti M Mäki Pirjo P Järvelin Marjo-Riitta MR Freimer Nelson N Peltonen Leena L Veijola Juha J Paunio Tiina T

BMJ open 20110827 1

Objectives Depression is a worldwide leading cause of morbidity and disability. Genetic studies have recently begun to elucidate its molecular aetiology. The authors investigated candidate genes of monoamine neurotransmission and early environmental risk factors for depressiveness in the genetically isolated population-based Northern Finland Birth Cohort 1966 (12 058 live births). Design The authors ascertained and subdivided the study sample (n=5225) based on measures of early development and ...[more]

PMID: 22021758

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Project description:BackgroundExtremely tall children (defined as height SDS (HSDS) ≥+3) are frequently referred to specialized healthcare for diagnostic work-up. However, no systematic studies focusing on such children currently exist. We investigated the aetiology, clinical features, and auxological clues indicative of syndromic tall stature in extremely tall children subject to population-wide growth monitoring and screening rules.MethodsSubjects with HSDS ≥+3 after three years of age born between 1990 and 2010 were identified from the Helsinki University Hospital district growth database. We comprehensively reviewed their medical records up to December 2020 and recorded underlying diagnoses, auxological data, and clinical features.FindingsWe identified 424 subjects (214 girls and 210 boys) who fulfilled the inclusion criteria. Underlying growth disorder was diagnosed in 61 (14%) patients, in 36 (17%) girls and 25 (12%) boys, respectively (P=0•15). Secondary causes were diagnosed in 42 (10%) patients and the two most frequent secondary diagnoses, premature adrenarche, and central precocious puberty were more frequent in girls. Primary disorder, mainly Marfan or Sotos syndrome, was diagnosed in 19 (4%) patients. Molecular genetic studies were used as a part of diagnostic work-up in 120 subjects. However, array CGH or next-generation sequencing studies were seldom used. Idiopathic tall stature (ITS) was diagnosed in 363 (86%) subjects, and it was considered familial in two-thirds. Dysmorphic features or a neurodevelopmental disorder were recorded in 104 (29%) children with ITS. The probability of a monogenic primary growth disorder increased with the degree of tall stature and deviation from target height.InterpretationA considerable proportion of extremely tall children have an underlying primary or secondary growth disorder, and their risk is associated with auxological parameters. Clinical features related to syndromic tall stature were surprisingly frequent in subjects with ITS, supporting the view that syndromic growth disorders with mild phenotypes may be underdiagnosed in extremely tall children. Our results lend support to comprehensive diagnostic work-up of extremely tall children.FundingPäivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, and Helsinki University Hospital research grants.

Dataset Information

Interaction of early environment, gender and genes of monoamine neurotransmission in the aetiology of depression in a large population-based Finnish birth cohort.

Publications

Interaction of early environment, gender and genes of monoamine neurotransmission in the aetiology of depression in a large population-based Finnish birth cohort.

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