Cohort Descriptives

Variable Response
Cohort name Generation Scotland: Scottish Family Health Study
Cohort acronym GS: SFHS
General Study Overview The aim of GS: SFHS is to establish a large, family-based intensively-phenotyped cohort recruited from the general population across Scotland, as a resource for studying the genetics of health areas of current and projected public health importance. It aims to identify genetic variants accounting for variation in levels of quantitative traits underlying the major common complex diseases (such as cardiovascular disease, cognitive decline, mental illness) in Scotland. DNA and non-identifiable information from this cohort will be made available to researchers in Scotland and international collaborators. Baseline data was collected at a single clinic visit. Longitudinal data is available by linkage to NHS medical records. Some participants are being invited to new clinic visits in 2015-17. This profile also includes scanning information from the Stratifying Resilience and Depression Longitudinally (STRADL) study to which approximately 3,000 GS participants have been invited for scanning.
Number of subjects at baseline 21476 plus 2484 postal participants (saliva for DNA, pre-clinic questionnaire, PCQ). 59% female..
Institution name Universities of Edinburgh, Aberdeen, Dundee and Glasgow and NHS Scotland
Department name Institute of Genetics & Molecular Medicine, University of Edinburgh
City Edinburgh
Study or database website

http://www.generationscotland.org/

Principal Investigator (PI): Name Prof David Porteous
PI: Address Medical Genetics Section, University of Edinburgh, IGMM, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU
PI: email

david.porteous@ed.ac.uk

PI: phone +44 (0)131 651 1040
Administrative Contact (AC): Name Archie Campbell
AC: Address Medical Genetics Section, University of Edinburgh, IGMM, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU
AC: email Archie.campbell@igmm.ed.ac.uk
AC: phone 0131 651 8740
Technical Contact/Data manager (TC): Name Archie Campbell
TC: Address Medical Genetics Section, University of Edinburgh, IGMM, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU
TC: email

archie.campbell@igmm.ed.ac.uk

TC: phone 0131 651 8740
Key study references

Open literature list

Population based study? Yes
Family based study? Yes
Clinical based sample? No
Is there follow-up data available? Yes
Were participants included prior to development of dementia (may refer to controls only)? Yes
Were participants included prior to development of MCI (may refer to controls only)? Yes
How is data collected? Postal
combination: Mostly by person, some people are contacted through post: 21476 plus 2484 postal participants.
Who carries out data collection? Interviewers
Clinical staff: Research nurses
Does this take place in participants' homes or at a central location? Central
Do participants take part individually or are families/partners involved? Individually
Family
Dementia cases ascertained as part of study: No
Diagnosis based on review of existing clinical data No
Was diagnosis/primary outcomes made blind to exposure variables? No
How many times followed up? 0
How regular is follow-up? Less often
Less often: Follow up is through NHS linkage data. However, some of the cohort have been invited into the Stratifying Resilience and Depression Longitudinally (STRADL) study that will involve MRI scans (approx 10% of the cohort).
Study start date 2006-01-23
Is study ongoing? Yes
Is study still recruiting? No
Inclusion criteria Originally, the team only recruited people with family members who would also take part. Probands increased to include aged 18+.
Exclusion criteria Unable to consent.

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Age at time of diagnosis of dementia No
Age at last follow-up Yes
Age at time of death Yes
Sex Yes
Ethnicity Yes
Education Yes
Physical examinations
Any physical examination performed? Yes
Blood pressure Data available
Assessed before onset of dementia
Weight Data available
Assessed before onset of dementia
Height Data available
Assessed before onset of dementia
Heart Rate Data available
Assessed before onset of dementia
Anthropometry Data available
Assessed before onset of dementia
Comments: Bioimpedence measure of body fat.
ECG Data available
Assessed before onset of dementia
Comments
Specific assessment of peripheral vascular disease Data available
Assessed before onset of dementia
Comments: ABPI: Blood pressure on ankle and arm and ratio worked out.
Spirometry Data available
Assessed before onset of dementia
Comments: Forced expiratory volume in 1 second, forced vital capacity, forced expiratory flow.
Medical conditions
Cardiovascular disease data Yes: If self-report in medical history.
Myocardial infarction Data available
Comments: If self-report in medical history.
Medication use for CVD Data available
Hypertension Data available: If self-report in medical history.
Systolic/diastolic BP Data available
Mean arterial pressure Data available
Virus testing No data available
Olfactory sensitivity No
Medication use Yes
Cancer Data available
Diabetic Status Data available

Cognitive Outcomes

Variable Response
Any domain-specific cognitive test performed? Yes
Verbal Memory Data available
Data available
N (estimate): 21316
List all tests: Weschler logical memory test immediate and delayed (WMS III UK, Weschler, 1998)
Pen and paper
Reaction time Data available
Data available
N (estimate): 1049
List all tests: Deary-Liewald CRT test (2011)
Computerised: Deary-Liewald reaction time task (Deary et al., 2011)
Language Data available
Data available
N (estimate): 21207 (Verbal Fluency) 21075 (Mill Hill vocabulary test)
List all tests: Verbal fluency (Lezak, 1995), Mill Hill Vocabulary Scale (Raven et al., 1977)
Pen and paper
Working memory Data available
Data available: Investigators report as 'Executive function'
N (estimate)
List all tests: Verbal fluency test (Lezak, 1995)
Pen and paper
Other cognitive tasks Wechsler digit symbol test (WAIS III, Wechsler, 1998) measure of speed of information processing
IQ data available? No
Cognitive background? Yes
Years of education Yes
Level of education Yes
Parental education No
Standard dementia global cognition scales? No
MMSE No
MoCA No
ADAS-Cog No
Addenbrooke's Cognitive Exam No
3MS No
GPCOG No

Non-Cognitive Clinical Outcomes

Variable Response
Dementia diagnosis
Alzheimer's dementia No
Lewy Body Disease No
Huntingtons Disease No
Parkinsons Disease No
Frontotemporal dementia No
Vascular dementia No
MCI No
Subjective complaint No
Dementia diagnosis (Other comments) Yes
Functional rating scales
Any information on dementia rating collected? No
PDQ39 (PD specific) No
UPDRS (PD specific) No
Hoehn and Yahr (PD specific) No
Schwab and England (PD specific) No
UHDRS (HD specific) No
Any information on subjective complaints collected? No
Any neuropsychiatric rating scale administered? Yes
Aggression Scale No
Beck Depression Inventory No
Behave-AD No
Center for Epidemiologic Studies Depression scale (CES-D) No
Connor-Davidson Resilience Scale No
Cornell depression Scale No
Geriatric Depression Scale (GDS) No
Hamilton depression rating scale (HDRS) No
Montgomery-Asberg depression scale (MADRS) No
NPI No
NPI-Q No
Speilberger State Anxiety Scale No
Hospital anxiety depression scale/psychiatry (HADS) No
Specify any other scales No
Any Quality of Life Data Colllected? No
Quality of Life-Alzheimers Disease (QOL-AD) No
Dementia Quality of Life Instrument (DEMQOL) No
Discomfort Scale for Dementia of Alzheimers Type (DS-DAT) No
Progressive Deterioration Scale (PDS) No
Quality of Life in Late-Stage Dementia Scale (QUALID) No
Bedfords Alzheimers Nursing Severity Scale(BANS-S) No
EQ-5DVAS No
Short Form (SF) 36 No
Health Utilities Index 1, 2 or 3 No
Any information on Caregivers and Caregiving Collected? No
Health service utilisation
Any Health Resource Utilisation Collected ? No
Hospital utilisation Yes
Prescription Medicine Cost No
Over the Counter Drug Costs No
Nursing Home Costs No
Costs of Visits to Specialists (out-patient) No
Costs of Home-Care No
Admission to nursing home No
Admission to home care No
Day care at nursing home No
Day care at home for elderly No
Home care- domestic No
Home care- personal care No
Home care- nursing No
Physical therapist No
Care of community mental health team No
Permanent stay at nursing home No
Informal ADL care No
Informal iADL care No
Days of work absence if having a paid job No
Other neurological or psychiatric measurements? Yes
Any stroke data? Yes
Stroke type No
Transient Ischemic Attack No
Carotid plaques No
Any head trauma data? No
Sports, soccer and boxing No
BISQ or equivalent No
EEG No
Psychiatric evaluations Yes
CESD scale (depression) No
Personality evaluation Yes
Personality evaluation comments Yes
Comments: Eysenck Personality Questionnaire Revised Short Form (Eysenck et al., 1985), Schizotypical personality questionnaire (SPQ-B) in Phase 2 PCQ only. Mood disorder questionnaire (MDQ), Phase 2 PCQ only.
Apathy evaluation No
Anxiety measure Yes
Resilience evaluation No

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? Scans done as part of the STRADL study and currently carried out at Aberdeen, planned to open for Edinburgh and Dundee. Imaging will open at other sites in Scotland. The MR data from the scanner will be copied to a dedicated folder on the central University server by radiographers. From the scanner console, data will be exported in enhanced DICOM format (multiframe DICOM), resulting in one file for each sequence. The fMRI log files will be copied in a big “Log_files” folder in “fMRI_log”. The big “Log_files” folder will contain also the logs from “Hot Cognitive Test”. Once the data has been checked it will be sent via rsync to Edinburgh. An md5 checksum will be generated for each verified enhanced DICOM file. These checksums and their linked files will then be tarred and compressed into a single archive. An md5 checksum of this archive will be generated and both will then be transferred via rsync to Edinburgh. An automated script will transfer the data. Verified data will be copied to an “Outgoing” STRADL folder in Edinburgh. This folder will be checked automatically and any new content will be copied via secure channel to Edinburgh. The status of the outgoing folder will be checked and if the transfer has failed it will retry automatically. An email will be sent every week by STRADL RF from Aberdeen to Edinburgh specifying the data which Edinburgh should have received from previous week. A confirmation email about receiving the data will be expected in Aberdeen too. Structure of the STRADL folder on the University server: After the “auto check” of the data, it will be stored automatically to the STRADL/MRI/Data/Primary primary folder in enhanced DICOM format (multiframe DICOM), this folder will be “read-only”.
Structural T1 Acquired
Acquired: As part of the STRADL study (also includes participants from ACONF).
N controls: 3,000 have been invited for scanning
Manufacturer: Philips
Scanner N: Single for now. Imaging will open at Dundee and Edinburgh.
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired: As part of the STRADL study (also includes participants from ACONF).
N controls: 3,000 have been invited for scanning
Manufacturer: Philips
Scanner N: Single for now. Imaging will open at Dundee and Edinburgh.
Field strength: 3T
Diffusion imaging (DTI/DWI) Acquired
Acquired: As part of the STRADL study (also includes participants from ACONF).
N controls: 3,000 have been invited for scanning
Manufacturer: Philips
Scanner N: Single for now. Imaging will open at Dundee and Edinburgh.
Field strengths: 3T
f-MRI (task) Acquired
Acquired: Reward task and Ekman fearful faces task. Scanning as s part of the STRADL study (also includes participants from ACONF).
N controls: 3,000 have been invited for scanning
Manufacturer: Philips
Scanner N: Single for now. Imaging will open at Dundee and Edinburgh.
Field strength: 3T
f-MRI (rest) Acquired
Acquired: Scanning as s part of the STRADL study (also includes participants from ACONF). No instructions, black screen with fixation cross throughout duration of scan (volumes = 195, 5mins 9s)
N controls: 3,000 have been invited for scanning
Model: Philips
Scanner N: Single for now. Imaging will open at Dundee and Edinburgh.
Field strength: 3T
PET Not acquired
Not acquired
SPECT Not acquired
Not acquired
MEG Not acquired
Not acquired
In vivo Spectroscopy Not acquired
Not acquired
Do you use an imaging data management system (e.g. XNAT or LORIS)? No
Primary contact for the technical aspects of the imaging data STRADL study contact, Dr Heather Whalley (Sibley): Heather.Whalley@ed.ac.uk

Genetics

Variable Response
Overview
Number Gwas subjects Controls N
Controls N: 20,128
Controls % male: 40% approx
Platform: Illumina OmniExpress Exome
Comments: Some of the participants might have a diagnosis, but this is unknown : Caucasian people genotyped only.
Gwas platform Illumina
HumanOmniExpress12v1: Illumina OmniExpress Exome
N imputed subjects Controls N
Controls N: Approx 20,000
Controls % male: 59%
Consortia: Haplotype Reference consortium
Comments: Caucasian people genotyped only.
Imputation reference panel 1000 Genomes Sanger HRC
N Exome Chip subjects Controls N
Controls N: Approx 20,000
Controls % male: Approx 40%
Comments: Caucasian people genotyped only.
ExomeChip versions Illumina OmniExpress Exome- same chip as the GWAS
N Whole Exome sequenced Controls N
Controls N: Approx 1,000
Controls % male: Approx 40%
Consortia: UK 10K
Comments: Caucasian people genotyped only.
Exome/Genome sequencing broad platform categories Illumina
N Whole genome sequenced Yes: Approx 20 people
Genome sequencing broad platform categories Illumina: Illumina X10 Genome Scotland partnership
N samples not sequenced or genotyped Controls N
Controls N: Approx 4,000. Including postal people.
Comments: Postal people have no clinical data available, less phenotype data. Caucasian people genotyped only.
N APOE genotyped Cases N
Cases N: Possible that some cases in this study
Controls N: Approx 24,000
Platform: TaqMan
Comments: Some SNPs relevant to APOE
N not APOE genotyped Cases N
Cases N: 0
Controls N: 0
Gene screening
APOE Yes
Estimated N: 24,000
TREM2 No
APP No
PSEN1 No
PSEN2 No
GRN No
MAPT No
C9ORF72 No
VCP No
CHMP2B No
TDP-43 No
PRNP No
SNCA No
LRRK2 No
PINK1 No
PARK2 No
PARK7 No
NOTCH3 No
CST3 No
TTR No
GSN No
ITM2B No
HTT No
NPC1 No
NPC2 No

Biological samples

Variable Response
Blood collected Yes
Plasma No
Serum Yes
Comments: Clot activator with gel separator for serum 3 x 5ml. Serum stored at -80.
RNA No
DNA Yes
Comments: EDTA 2 x 4.7 ml, 1 x 9ml or saliva
Abeta 1-40 No
Abeta 1-42 No
Abeta x-40 No
Abeta x-42 No
Blood Metabolic Analytes
CRP (c-reactive protein) No
eGFR (estimated Glomular Filtration Rate) Yes
Glucose Yes
HbA1c No
Lipids No
Liver Function Tests No
Serum creatinine Yes
Homocysteine No
Folate No
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine Yes
Details: Stored at -80 degrees for future proteomics analysis. Some analysis has been done: uromodulin and kidney function.
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Subgroup
Details: Postal people (approx 2,500) plus people from whom bloody could not be obtained. Used for DNA.
Cortisol No
Are laboratory protocols and saliva storage information available? No
CSF
CSF collected No
Are CSF laboratory protocols and storage information available? No
mtDNA abnormalities No
Oxidative stress No

Brain donation

Variable Response
Is brain donation part of the existing protocol? No
Are information sheets made available to representative or consultees? No
Are retrospective interviews carried out after the participant's death? No
Is there a procedure for declining donation/failed recruitment/project termination? No
Has an actuarial analysis been completed? No

Lifestyle

Variable Response
Smoking Yes
Pack years Data available
Passive smoking Data available
Current smoking Data available
Former smoking Data available
Alcohol Data available
Units per day/week vs weekend Data available
Specified beverage type (wine, spirits, beers) Data available
Comments: For some participants
Abstainers/former users Data available
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Hip/waist circumference Data available
Fat percentage Data available: Bioimpedence
Metabolic syndrome Data available
Type of exercise: heavy, light Data available
Occupation possible job matrices Data available
Diet Yes
Carbs, protein, fats, fish oil Data available
Food questionnaires Data available
Comments
Other dietary items Yes
Employment status
Employment status Data available
Comments: Occupation recorded
Living situation
Living situation Data available
Socioeconomic status
Socioeconomic status measures Data available
Comments: Postcode and Scottish index of multiple deprivation.
Sleep assessment

Ethics and Engagement

Variable Response
Participant engagement
Is there participant representation in the governance of the cohort? No
Do existing mechanisms for consulting/involving participants exist? No
If so, does this happen on an ongoing or an ad hoc basis? NA
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? A member of the NHS Lothian Bioresources Team accesses the committee on governance. The study team reports annually to the Research Tissue Bank Ethics Committee.
If yes, who is represented on it? A member of the NHS Lothian Bioresources Team.
Does the cohort include participants who lack capacity? No
Is there a process in place for participants who lose capacity? No
Do participants provide contact information for a person to act as a potential consultee? No
Disclosure
Do procedures exist for the disclosure of incidental findings? Yes
What kinds of finding do these relate to? (imaging, genotyping, etc) Anything clinically relevant, for example, blood pressure. For genetics data, they would take guidance from the REC.
Specified in the consent form that they would absolutely not report any incidental findings around parentage.
Who is responsible for disclosing incidental findings? GP
Do procedures exist for the disclosure of clinically relevant information identified as a direct focus of the study? (e.g. a diagnosis of dementia) No
Recruitment
How was the cohort recruited (NHS or not, primary or secondary care)? Primarily through NHS primary care. Recruitment of GP practices facilitated through Scottish Practices and Professionals Involved in Research (SPPIRe). Participants were identified through the Community Health Number (CHI).
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? Yes
Consent and recontact
Is there consent for recontact? Yes
If so, under what conditions? "I consent to being contacted in the future by the SFHS team to discuss possible participation in further research arising directly from this study. I affirm that this will not commit me in any way to taking part in further research."

Data Management

Variable Response
Consent for linkage to routine data
Which parts of the UK are represented by participants in your cohort? Scotland
Scotland