Cohort Profile: Stratifying Resilience and Depression Longitudinally (STRADL): a questionnaire follow-up of Generation Scotland: Scottish Family Health Study (GS:SFHS)

Navrady, Lauren; Wolters, Maria; MacIntyre, Donald J.; Clarke, Toni‐Kim; Campbell, Archibald; Murray, Alison; Evans, Kathryn; Seckl, Jonathan R.; Haley, C.S.; Milburn, Keith; Wardlaw, Joanna M.; Porteous, David J.; Deary, Ian J.; McIntosh, Andrew M.

doi:10.1093/ije/dyx115

Cited by 73 publications

(85 citation statements)

References 27 publications

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“…The procedures and details for DNA extraction and genotyping have been extensively described elsewhere 55,56 . 21 525 participants were re-contacted to participate in a follow-up mental health study (Stratifying Resilience and Depression Longitudinally, STRADL), of which 8 541 participants responded providing updated measures in psychiatric symptoms and SLE through self-reported mental health questionnaires 57 . Samples were excluded if: they were duplicate samples, had diagnoses of bipolar disorder, no SLE data (non-respondents), were population outliers (mainly non-Caucasians and Italian ancestry subgroup), had sex mismatches, or were missing more than 2% of genotypes.…”

Section: Cohort Descriptionsmentioning

confidence: 99%

“…SNPs were excluded if: missing more than 2% of genotypes, Hardy-Weinberg Equilibrium test p < lxlCf 6 , or minor allele frequency less than 1%. Further details of the GS and STRADL cohort are available elsewhere 53,57-59 . All components of GS and STRADL obtained ethical approval from the Tayside Committee on Medical Research Ethics on behalf of the NHS (reference 05/sl401/89).…”

Section: Cohort Descriptionsmentioning

confidence: 99%

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Genome-wide by environment interaction studies (GWEIS) of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Soler

Macdonald-Dunlop

Adams

et al. 2018

Preprint

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Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77×10-6). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53kb downstream PIWIL4; p = 4.95×10-9; total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46×10-8; dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00×10-8; dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77×10-6). Polygenic risk scores (PRS) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91×10-3). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions.

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Section: Cohort Descriptionsmentioning

confidence: 99%

Section: Cohort Descriptionsmentioning

confidence: 99%

Genome-wide by environment interaction studies (GWEIS) of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Soler

Macdonald-Dunlop

Adams

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…The procedures and further details for DNA extraction and genotyping have been extensively described elsewhere 32,33 . In 2014, 21 525 participants from Generation Scotland eligible for re-contact were sent self-reported questionnaires as part of a further longitudinal assessment funded by a Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) 34 to collect new and updated mental health questionnaires including psychiatric symptoms and SLE measures. 9 618 re-contacted participants from Generation Scotland agreed to provide new measures to the mental health follow-up 34 (44.7% response rate).…”

Section: Methodsmentioning

confidence: 99%

A validation of the diathesis-stress model for depression in Generation Scotland

Arnau‐Soler

Adams

Clarke

et al. 2018

Preprint

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Depression has well-established influences from genetic and environmental risk factors. This has led to the diathesis-stress theory, which assumes a multiplicative gene-by-environment interaction (GxE) effect on risk. Recently, Colodro-Conde et al. empirically tested this theory, using the polygenic risk score for major depressive disorder (PRS, genes) and stressful life events (SLE, environment) effects on depressive symptoms, identifying significant GxE effects with an additive contribution to liability. We have tested the diathesis-stress theory on an independent sample of 4 919 individuals.We identified nominally significant positive GxE effects in the full cohort (R2 = 0.08%, p = 0.049) and in women (R2 = 0.19%, p = 0.017), but not in men (R2 = 0.15%, p = 0.07). GxE effects were nominally significant, but only in women, when SLE were split into those in which the respondent plays an active or passive role (R2 = 0.15%, p = 0.038; R2 = 0.16%, p = 0.033, respectively). High PRS increased the risk of depression in participants reporting high numbers of SLE (p = 2.86 × 10−4). However, in those participants who reported no recent SLE, a higher PRS appeared to increase the risk of depressive symptoms in men (β = 0.082, p = 0.016) but had a protective effect in women (β = −0.061, p = 0.037). This difference was nominally significant (p = 0.017). Our study reinforces the evidence of additional risk in the aetiology of depression due to GxE effects. However, larger sample sizes are required to robustly validate these findings.

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“…5 A subset of participants was selected for genotyping, consisting of those individuals who were born in the UK, had Caucasian ethnicity, had full baseline phenotype data available from a visit to a GS:SFHS research clinic in Aberdeen, Dundee, Glasgow or Perth, and had consented for their data to be linked to their NHS records. 5,11 The Data can therefore be accessed for most participants from well before the period of recruitment to the GS:SFHS cohort (2006-2011) and subsequent to participation in the study, up to within a few months of the date of a data release. The resource includes contemporary measures that reflect current tests and treatments.…”

Section: Methodsmentioning

confidence: 99%

Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants

Kerr

Campbell

Marten

et al. 2017

Preprint

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This paper provides the first detailed demonstration of the research value of the Electronic Health Record (EHR) linked to research data in Generation Scotland Scottish Family Health Study (GS:SFHS) participants, together with how to access this data. The structured, coded variables in the routine biochemistry, prescribing and morbidity records in particular represent highly valuable phenotypic data for a genomics research resource. Access to a wealth of other specialized datasets including cancer, mental health and maternity inpatient information is also possible through the same straightforward and transparent application process. The Electronic Health Record linked dataset is a key component of GS:SFHS, a biobank conceived in 1999 for the purpose of studying the genetics of health areas of current and projected public health importance. Over 24,000 adults were recruited from 2006 to 2011, with broad and enduring written informed consent for biomedical research. Consent was obtained from 23,603 participants for GS:SFHS study data to be linked to their Scottish National Health Service (NHS) records, using their Community Health Index (CHI) number. This identifying number is used for NHS Scotland procedures (registrations, attendances, samples, prescribing and investigations) and allows healthcare records for individuals to be linked across time and location. Here, we describe the NHS EHR dataset on the sub-cohort of 20,032 GS:SFHS participants with consent and mechanism for record linkage plus extensive genetic data. Together with existing study phenotypes, including family history and environmental exposures such as smoking, the EHR is a rich resource of real world data that can be used in research to characterise the health trajectory of participants, available at low cost and a high degree of timeliness, matched to DNA, urine and serum samples and genomewide genetic information.

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Cohort Profile: Stratifying Resilience and Depression Longitudinally (STRADL): a questionnaire follow-up of Generation Scotland: Scottish Family Health Study (GS:SFHS)

Cited by 73 publications

References 27 publications

Genome-wide by environment interaction studies (GWEIS) of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

Genome-wide by environment interaction studies (GWEIS) of depressive symptoms and psychosocial stress in UK Biobank and Generation Scotland

A validation of the diathesis-stress model for depression in Generation Scotland

Electronic Health Record and Genome-wide Genetic Data in Generation Scotland Participants

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