Dataset Information

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank.

ABSTRACT: Genome-wide association studies using genotype data have had limited success in the identification of variants associated with major depressive disorder (MDD). Haplotype data provide an alternative method for detecting associations between variants in weak linkage disequilibrium with genotyped variants and a given trait of interest. A genome-wide haplotype association study for MDD was undertaken utilising a family-based population cohort, Generation Scotland: Scottish Family Health Study (n?=?18,773), as a discovery cohort with UK Biobank used as a population-based replication cohort (n?=?25,035). Fine mapping of haplotype boundaries was used to account for overlapping haplotypes potentially tagging the same causal variant. Within the discovery cohort, two haplotypes exceeded genome-wide significance (P?

SUBMITTER: Howard DM

PROVIDER: S-EPMC5802488 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank.

Howard David M DM Hall Lynsey S LS Hafferty Jonathan D JD Zeng Yanni Y Adams Mark J MJ Clarke Toni-Kim TK Porteous David J DJ Nagy Reka R Hayward Caroline C Smith Blair H BH Murray Alison D AD Ryan Niamh M NM Evans Kathryn L KL Haley Chris S CS Deary Ian J IJ Thomson Pippa A PA McIntosh Andrew M AM

Translational psychiatry 20171130 11

Genome-wide association studies using genotype data have had limited success in the identification of variants associated with major depressive disorder (MDD). Haplotype data provide an alternative method for detecting associations between variants in weak linkage disequilibrium with genotyped variants and a given trait of interest. A genome-wide haplotype association study for MDD was undertaken utilising a family-based population cohort, Generation Scotland: Scottish Family Health Study (n = 1 ...[more]

PMID: 29187746

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Project description:BACKGROUND.:Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. METHODS.:Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457-14,836, age 45-81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use. RESULTS.:Lifetime MDD was robustly associated with a lower g-factor (? = -0.10, PFDR = 4.7 × 10-5), with impairments in attention, processing speed, and executive functioning (? ? 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (? = -0.18, PFDR = 7.5 × 10-5). CONCLUSIONS.:Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.

Dataset Information

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank.

Publications

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank.

Similar Datasets

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