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Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19?762), UK Biobank (n=24?048) and the English Longitudinal Study of Ageing (n=5766).

ABSTRACT: Major depressive disorder (MDD) is a heritable and highly debilitating condition. It is commonly associated with subcortical volumetric abnormalities, the most replicated of these being reduced hippocampal volume. Using the most recent published data from Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium's genome-wide association study of regional brain volume, we sought to test whether there is shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and MDD. We explored this using linkage disequilibrium score regression, polygenic risk scoring (PRS) techniques, Mendelian randomisation (MR) analysis and BUHMBOX. Utilising summary statistics from ENIGMA and Psychiatric Genomics Consortium, we demonstrated that hippocampal volume was positively genetically correlated with MDD (rG=0.46, P=0.02), although this did not survive multiple comparison testing. None of the other six brain regions studied were genetically correlated and amygdala volume heritability was too low for analysis. Using PRS analysis, no regional volumetric PRS demonstrated a significant association with MDD or recurrent MDD. MR analysis in hippocampal volume and MDD identified no causal association, however, BUHMBOX analysis identified genetic subgrouping in GS:SFHS MDD cases only (P=0.00281). In this study, we provide some evidence that hippocampal volume and MDD may share genetic architecture in a subgroup of individuals, albeit the genetic correlation did not survive multiple testing correction and genetic subgroup heterogeneity was not replicated. In contrast, we found no evidence to support a shared genetic architecture between MDD and other regional subcortical volumes or ICV.

SUBMITTER: Wigmore EM

PROVIDER: S-EPMC5611720 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19 762), UK Biobank (n=24 048) and the English Longitudinal Study of Ageing (n=5766).

Wigmore E M EM Clarke T-K TK Howard D M DM Adams M J MJ Hall L S LS Zeng Y Y Gibson J J Davies G G Fernandez-Pujals A M AM Thomson P A PA Hayward C C Smith B H BH Hocking L J LJ Padmanabhan S S Deary I J IJ Porteous D J DJ Nicodemus K K KK McIntosh A M AM

Translational psychiatry 20170815 8

Major depressive disorder (MDD) is a heritable and highly debilitating condition. It is commonly associated with subcortical volumetric abnormalities, the most replicated of these being reduced hippocampal volume. Using the most recent published data from Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium's genome-wide association study of regional brain volume, we sought to test whether there is shared genetic architecture between seven subcortical brain volumes and intra ...[more]

PMID: 28809859

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Project description:BackgroundDepressive symptoms and physical performance are inversely associated, but it is unclear whether their association is bidirectional. We examined whether the association between depressive symptoms and physical performance measured using gait speed is bidirectional.MethodsWe used a national sample of 4,581 community-dwelling people aged 60 years and older from the English Longitudinal Study of Ageing (from 2002-03 to 2008-09). We fitted Generalized Estimating Equation (GEE) regression models to analyse repeated measurements of gait speed (m/sec) and elevated depressive symptoms (defined as a score of ?4 on the eight-item Center for Epidemiological Studies-Depression scale).ResultsSlower gait speed was associated with elevated depressive symptoms both concurrently and two years later. After adjustment for previous depressive symptoms and sociodemographic, clinical, lifestyle, psychosocial, and cognitive factors the concurrent association was partially explained (Odds Ratio [OR] 0.42, 95% confidence interval [CI], 0.30 to 0.59, per 1m/sec increase in gait speed) and the two-year lagged association fully (OR 0.75, 95% CI, 0.56 to 1.00). Elevated depressive symptoms were associated with slower gait speed. Full adjustment for covariates (including previous gait speed) partially explained both the concurrent (? regression coefficient [?] -0.038, 95% CI, -0.050 to -0.026, for participants with elevated depressive symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.017, 95% CI, -0.030 to -0.005). Subthreshold depressive symptoms (defined as a score of two or three on the eight-item Center for Epidemiological Studies-Depression scale) were also associated with slower gait speed. Full adjustment for covariates partially explained both the concurrent (? -0.029, 95% CI, -0.039 to -0.019, for participants with subthreshold symptoms compared with those with no or one symptom) and the two-year lagged associations (? -0.011, 95% CI, -0.021 to -0.001).ConclusionsThe inverse association between gait speed and depressive symptoms appears to be bidirectional.

Project description:AimAs sport and physical activity are vital to support extended health spans, this study aimed to analyse the current trends in sports participation and physical activity rates among individuals aged 65 years and older in Scotland. Data were compared with the Chief Medical Officer (CMO) guidelines and analysed the influence of key factors on participation rates.MethodsThe study used data from the Scottish Health Survey and the Scottish Household Survey (2019) to investigate self-reported participation in physical activity and sports across different age groups. Descriptive statistics and cross-tabulations were used to analyse the relationships between participation rates and influencing factors. Participation data for Parkrun events in Scotland were also analysed for the years 2008-2018.ResultsThe study found a clear decline in sports participation with age, with a steep decline after the age of 65, particularly in women. The majority of participation among individuals aged 65+ was in walking, with a sport participation rate of only 31.2% when walking was excluded. Physical activity and sport participation was lower in women across all age ranges but particularly so in the 75+ age group. The most popular sporting activities in the older age group were keep fit/aerobics, swimming and golf. Additionally, the study found that social deprivation had a major impact on sports participation rates, with the most deprived households exhibiting the lowest participation levels irrespective of age. The prevalence of loneliness was lower among individuals who participated in sports or adhered to the CMO guidelines for moderate/vigorous physical activity and strength-building exercises.DiscussionThe findings of this study have implications for promoting physical activity and sports participation among older adults, particularly in deprived communities. This study highlights the importance of balance exercises within sport and the need for more targeted efforts to increase participation rates among older adults. The study also emphasizes the positive impact of sports participation on reducing loneliness among older adults. Overall, the findings suggest the need for ongoing efforts to promote physical activity and sports participation among older adults to improve their overall health and well-being.

Dataset Information

Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19?762), UK Biobank (n=24?048) and the English Longitudinal Study of Ageing (n=5766).

Publications

Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19 762), UK Biobank (n=24 048) and the English Longitudinal Study of Ageing (n=5766).

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