Cohort Descriptives

Variable Response
Cohort name UK Biobank
Cohort acronym UK Biobank
General Study Overview UK Biobank aims to assess the relevance of a very wide range of exposures on a very wide range of health-related outcomes. It is a large prospective study to investigate the role of genetic factors, environmental exposures and lifestyle in the causes of major diseases of late and middle age.
During 2006-2010, UK Biobank conducted its recruitment phase of more than 500,000 participants who gave their consent, answered questions, had physical measurements and gave samples (blood, urine and saliva) at a baseline assessment visit. Follow-up of their health is now being conducted through medical and other health-related records. Access systems have been developed to facilitate use of the UK Biobank Resource by bona fide researchers for health-related research that is in the public interest.
NB: Due to the size and complexity of Biobank and the comprehensiveness of the Biobank website, much additional information is available in the Documents section of this profile, or in hyperlinks embedded within the cohort profile.
Publications can be seen here: http://www.ukbiobank.ac.uk/published-papers/
Number of subjects at baseline 503, 316
Institution name UK Biobank
Department name UK Biobank Coordinating Centre
City Stockport
Study or database website

https://www.biobank.ac.uk

Principal Investigator (PI): Name Prof Sir Rory Collins
PI: Address Prof Rory Collins, UK Biobank Principal Investigator & Chief Executive Officer, 1-2 Spectrum Way, Adswood, Stockport, SK3 0SA
PI: email

Chief Scientist, Cathie Sudlow: cathie.sudlow@ed.ac.uk

PI: phone 0800 0 276 276
Administrative Contact (AC): Name Ms Robin Flaig
AC: Address Robin Flaig: CCBS, Chancellor's Building, Royal Infirmary of Edinburgh, Edinburgh, UK Biobank Coordinating Centre, 1-2 Spectrum Way, Adswood, Stockport, Cheshire, SK3 0SA.
AC: email Enquiries@ukbiobank.ac.uk, robin.flag@ed.ac.uk
AC: phone 0800 0 276 276
Technical Contact/Data manager (TC): Name Access Team
TC: Address UK Biobank Coordinating Centre, Access Team, Units 1 & 2 Spectrum Way, Adswood, Stockport, Cheshire SK3 0SA.
TC: email

access@ukbiobank.ac.uk

TC: phone 0800 0 276 276
Key study references

Open literature list

Population based study? Yes
Family based study? No
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? Combination
Who carries out data collection? Interviewers
Clinical staff: Key staff are research nursing and technical staff.
Does this take place in participants' homes or at a central location? Home
Central: Baseline visit at central location (office space). Pedometry (100,000) and emailed questionnaires (300,000) sent to participants and carried out at home. There are additional web based questionnaires that will also be carried out at home.
Do participants take part individually or are families/partners involved? Individually
Dementia cases ascertained as part of study: No
How regular is follow-up? Subgroups may be followed more frequently.
Study start date 2006-01-01
Is study ongoing? Yes
Is study still recruiting? No
Inclusion criteria Age 40-69 years.
Capacity to consent.
Lived within 20-25 miles of one of the assessment centres.
Exclusion criteria UK Biobank did not enrol potential participants who express the view that they would 
want to be withdrawn should they lose mental capacity or die because this would reduce 
the  value  of the  resource for research.

Demographic and Clinical Information

Variable Response
Demographics
Age Yes
Age at time of diagnosis of dementia Yes
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
Neurological examination Comments: Brain imaging MR study, see Imaging section of cohort profile. Full neurological examination not carried out however.
Heart Rate Data available
Assessed before onset of dementia
Anthropometry Data available
Assessed before onset of dementia
Comments: Height, Weight, waist circumference, hip circumference, bioimpedence measures.
ECG Data available
Assessed before onset of dementia
Respiratory examination Data available
Assessed before onset of dementia
PEFR Data available
Assessed before onset of dementia
Spirometry Data available
Assessed before onset of dementia
Gait assessment Data available
Assessed before onset of dementia
Comments: Self-report about gait, no objective measure.
Opthalmic examination Data available
Assessed before onset of dementia
Comments: 117,649 people took part in the eye and vision component of UK Biobank, undergoing modified logMAR visual acuity testing on a computerized system developed specifically for UK Biobank, autorefraction and keratometry (Tomey RC-5000), as well as measurement of intraocular pressure on a Reichert ORA Ocular Response Analyser, which returns measures of Goldmannequivalent intraocular pressure (IOP), corneal hysteresis, corneal resistance factor and IOP adjusted for corneal biomechanical properties. A smaller number (68,151) underwent simultaneous colour retinal photography, together with spectral domain optical coherence tomography (SD-OCT) in both eyes. These features, together with accompanying extensive phenotyping of all major organ systems, make the UK Biobank eye and vision dataset unique worldwide.
Acuity Data available
Assessed before onset of dementia
Comments: 117,649 people took part in the eye and vision component of UK Biobank, undergoing modified logMAR visual acuity testing on a computerized system developed specifically for UK Biobank, autorefraction and keratometry (Tomey RC-5000), as well as measurement of intraocular pressure on a Reichert ORA Ocular Response Analyser, which returns measures of Goldmannequivalent intraocular pressure (IOP), corneal hysteresis, corneal resistance factor and IOP adjusted for corneal biomechanical properties. A smaller number (68,151) underwent simultaneous colour retinal photography, together with spectral domain optical coherence tomography (SD-OCT) in both eyes. These features, together with accompanying extensive phenotyping of all major organ systems, make the UK Biobank eye and vision dataset unique worldwide.
Specify any others See data showcase: http://www.ukbiobank.ac.uk/data-showcase/
Medical conditions
Cardiovascular disease data Yes
Myocardial infarction Data available
Medication use for CVD Data available
Hypertension Data available
Systolic/diastolic BP Data available
Mean arterial pressure Data available
Hypotension Data available
Hypercholesterolemia Yes
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
Visual Memory Data available
Data available
N (estimate) : 3,718
Comments: http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100026
List all tests: This category contains data on a test designed to assess visual short-term memory, as part of the touchscreen questionnaire. The participant is shown a series of pictures of houses which have some windows lit. The participant then has to indicate which windows were lit after a 10-second delay. The data recorded include the number of columns and rows that were lit in each round of the test, the pattern of lights and the pattern of lights as remembered, and the time taken to complete the test. This test was performed in the pilot phase of the study and is available for a subset of participants.
Computerised: Touchscreen testing (Biobank).
Verbal Memory Data available
Data available: Planned Verbal Declarative Memory test.
N (estimate): 100,000 projected for 8-14 year imaging follow up.
Visuospatial Function Data available
Data available
N (estimate): 498,491
Comments: http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100026
List all tests: This category contains data on 'pairs' matching tests. Participants are asked to memorise the position of as many matching pairs of cards as possible. The cards are then turned face down on the screen and the participant is asked to touch as many pairs as possible in the fewest tries.
Computerised: Touchscreen testing (Biobank).
Attention Data available
Data available
N (estimate): 140,000 people at 7 year follow up online test and is planned for 8-14 year imaging study follow up, N=100,000.
List all tests: Trail making.
Reaction time Data available
Data available
N (estimate): 452,000 at baseline, 20,000 at year 5, 140,000 at 7 year online follow up, 100,000 projected for 8-14 year imaging follow up.
Comments: http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100026
List all tests: This category contains data on a test to assess reaction time and is based on 12 rounds of the card-game 'Snap'. The participant is shown two cards at a time, if both cards are the same, they press a button-box that is on the table in front of them as quickly as possible. For each of the 12 rounds, the following data were collected: the pictures shown on the cards (Index of card A, Index of card B), the number of times the participant clicked the 'snap' button, and the time it took to first click the 'snap' button.
Computerised: Touchscreen testing (Biobank).
Working memory Data available
Data available
N (estimate): 115,000 at baseline, 20,000 at year 5, 140,000 at 7 year online follow up, 100,000 projected for 8-14 year imaging follow up.
Comments: http://biobank.ctsu.ox.ac.uk/crystal/field.cgi?id=4282
List all tests: This category contains data on a test designed to assess numeric short-term memory, as part of the touchscreen questionnaire. The participant was shown a 2-digit number to remember. The number then disappeared and after a short while they were asked to enter the number onto the screen. The number became 1-digit longer each time they remembered correctly (up to a maximum of 12 digits). Data collected include the number of digits and value of the number, the length of time the number was displayed, the time that the participant first entered and last entered a digit, the time taken to complete the test, the value of the number entered by the participant, whether or not the participant was correct, the maximum number of digits remembered, and whether the test was completed. This test is available for a subset of participants.
Computerised: Touchscreen testing (Biobank).
Latent memory Data available
Data available
N (estimate): 187,179
List all tests: This category contains data on a question designed to assess 'Prospective Memory'. Early in the touchscreen cognitive section, the participant is shown the mesage "At the end of the games we will show you four coloured shapes and ask you to touch the Blue Square. However, to test your memory, we want you to actually touch the Orange Circle instead." This category includes data on the first and final answer, the history of attempts and the time it took to answer.
Computerised: Touchscreen testing (Biobank).
Other cognitive tasks Nonverbal reasoning (matrix) planned for 8-14 year imaging study follow up, N=100,000.
Digit-symbol substitution planned for 8-14 year imaging study follow up, N=100,000.
IQ data available? Yes
NART No
IQ other (list) Touchscreen baseline assessment centre test of fluid intelligence. N=115,000 at baseline, 20,000 at year 5, 140,000 at 7 year online follow up.
NIH Crystallised vocabulary planned for 8-14 year imaging follow up, N=100,000.
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 Yes
Lewy Body Disease Yes
Huntingtons Disease Yes
Parkinsons Disease Yes
Frontotemporal dementia Yes
Vascular dementia Yes
MCI No
Subjective complaint No
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? Yes
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
Specify any other quality of life scales Touchscreen questionnaire contains Psychosocial and Lifestyle and Environment questions. See Data Showcase: http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100025.
Life Events
• Childhood Trauma Screen (CTS)
• Adulthood Questions (based on national crime survey and SELCOH questions)
• PTSD Checklist -5 (PCL-5)
(see attached Mental Health Screening list).
Any information on Caregivers and Caregiving Collected? No
Caregivers for Alzheimers disease Problems Scale (CAPS) No
Community Dementia Quality of Life Profile (CDQLP) No
COQoL-AD No
Dementia Management Strategies Scale (DMSS) No
Caregiver Activity Survey (CAS) No
Quality of life of caregivers (CQOL) No
Screen for Caregiver Burden/Time Spent Caregiving (TSC) No
Work Productivity and Activity Impairment Questionnaire-dyad version (WPAI-DYAD) No
Zairit Burden No
Health service utilisation
Any Health Resource Utilisation Collected ? Yes
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 Yes
Transient Ischemic Attack Yes
Carotid plaques Yes
Any head trauma data? Yes
Loss of consciousness Yes
Sports, soccer and boxing No
Head trauma severity No
BISQ or equivalent No
EEG No
Psychiatric evaluations Yes
CESD scale (depression) No
Personality evaluation Yes
Apathy evaluation Yes
Anxiety measure Yes
Resilience evaluation Yes

Imaging

Variable Response
For imaging data, what format(s) do you use for storing data? Biobank store the data in DICOM but are also performing some post-processing on the images and the resulting images may therefore be NIFTI. Both DICOM and NIFTI files will be stored.
Structural T1 Acquired
Acquired: Feasibility study so far, larger imaging study planned. T1w 1x1x1mm, 5mins 3D MPRAGE, sagittal, iPat=2, Z-FoV=256mm (including neck)
N controls: 5,000 in feasibility study.
Acquisition period: 2015
Manufacturer: Siemens
Model: Skyra 32-channel RF coil
Scanner N: Single Siemens Skyra in Stockport. Funding permitted, two more scan centres will open, each with another Skyra.
Field strength: 3T
Fluid attenuation inversion recovery (FLAIR) Acquired
Acquired: T2 FLAIR 1.05x1x1mm, 6mins. iPat=2, 6/8 partial Fourier, 3D sagittal.
N controls: 5,000 in feasibility study,
Acquisition period: 2015
Manufacturer: Siemens
Model: Skyra
Scanner N: Single Siemens Skyra in Stockport. Funding permitted, two more scan centres will open, each with another Skyra.
Field strength: 3T
Diffusion imaging (DTI/DWI) Acquired
Acquired: Diffusion MRI 2x2x2mm, 2 shells (1000+2000), 100 directions, 7mins no within-slice acceleration, multiband x3 50 directions at b=1000 + 50 directions at b=2000 + 10 x b=0 b=0 AP-PA pairs also used to generate B0 fieldmap.
N controls: 5,000 in feasibility study.
Acquisition period: 2015
Manufacturer: Siemens
Model: Skyra
Scanner N: Single Siemens Skyra in Stockport. Funding permitted, two more scan centres will open, each with another Skyra.
Field strengths: 3T
f-MRI (task) Acquired
Acquired: 2.4x2.4x2.4mm, 4mins emotion faces task with visual+motor no within-slice acceleration, multiband x8, TR=0.73s.
N controls: 5,000 in feasibility study.
Acquisition period: 2015
Manufacturer: Siemens
Model: Skyra
Scanner N: Single Siemens Skyra in Stockport. Funding permitted, two more scan centres will open, each with another Skyra.
Field strength: 3T
f-MRI (rest) Acquired
Acquired: 2.4x2.4x2.4mm, 6mins no within-slice acceleration, multiband x8, TR=0.73s.
N controls: 5,000 in feasibility study.
Acquisition period: 2015
Manufacturer: Siemens
Model: Skyra
Scanner N: Single Siemens Skyra in Stockport. Funding permitted, two more scan centres will open, each with another Skyra.
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
Other (please specify) Protocol (total = 36mins). The ordered list of scans is:

Setup + shim + DOT-scout, 2mins.

T1w 1x1x1mm, 5mins
3D MPRAGE, sagittal, iPat=2, Z-FoV=256mm (including neck).

Resting-fMRI 2.4x2.4x2.4mm, 6mins
no within-slice acceleration, multiband x8, TR=0.73s.

Task-fMRI 2.4x2.4x2.4mm, 4mins
emotion faces task with visual+motor
no within-slice acceleration, multiband x8, TR=0.73s.

T2 FLAIR 1.05x1x1mm, 6mins
iPat=2, 6/8 partial Fourier, 3D sagittal.

Diffusion MRI 2x2x2mm, 2 shells (1000+2000), 100 directions, 7mins
no within-slice acceleration, multiband x3
50 directions at b=1000 + 50 directions at b=2000 + 10 x b=0
b=0 AP-PA pairs also used to generate B0 fieldmap.

SWI 0.8x0.8x3mm, 3D, 2 echos, 2mins 30s
saving out mag+phase for all coils separately.
Note:

ASL multi-TI, 2mins - about to be piloted, potentially associated with 50% reduction in task-fMRI time.

B0 Fieldmap 3x3x3mm, 1:15min - removed because we are using blip-reversed diffusion data instead, to estimate fieldmap.

T2 2D TSE, 0.9x0.9x5mm, 1min - removed due to overall timing constraints.
Do you use an imaging data management system (e.g. XNAT or LORIS)? No
Primary contact for the technical aspects of the imaging data Steve Garrett steve.garratt@ukbiobank.ac.uk
Retinal imaging Data available
Comments: 68,544 participants underwent retinal fundus camera imaging—a single non-mydriatic digital image was obtained from right and left eyes using a Topcon 3D OCT 1000 Mark 2 (45° field-of-view, centred to include both optic disc and macula). Colour images were stored in PNG format with dimensions 2048 × 1536 pixels.
OCT Data available
Comments: 68,544 participants underwent retinal fundus camera imaging—a single non-mydriatic digital image was obtained from right and left eyes using a Topcon 3D OCT 1000 Mark 2 (45° field-of-view, centred to include both optic disc and macula). Colour images were stored in PNG format with dimensions 2048 × 1536 pixels.

Genetics

Variable Response
Overview
Number Gwas subjects Controls N
Controls N: Approx 500,000.
Platform
Comments: Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants, the remaining 450,000 participants are currently being genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content). GWAS markers were selected using Affymetrix’ imputation-aware marker choice algorithms to provide genome-wide coverage in European ancestry populations of common (EMAF ≥5%, including the set of 246,055 markers on Axiom® Biobank Genotyping Array, DataSheet 1 2 P/N 902186) and low-frequency (1%< EMAF <5%) markers using the EUR panel defined as the GBR, CEU, FIN, IBS, and TSI samples from the KGP. See Data Showcase http://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100314.
Gwas platform Affymetrix: Genotype data will be available for all 500,000 participants in the UK Biobank cohort. Genotyping has been performed using the Affymetrix UK BiLEVE Axiom array on an initial 50,000 participants, the remaining 450,000 participants are currently being genotyped using the Affymetrix UK Biobank Axiom® array. The two arrays are extremely similar (with over 95% common content).
N imputed subjects Controls N
Controls N: 500,000
Comments: Imputation was carried out in chunks of 2Mb with a 250kb buffer region. A set of 2,000 haplotype copying states were used to impute each sample. Imputed variants in each non-overlapping part of each chunk were concatenated into per-chromosome files. Imputation-aware marker selection Affymetrix utilized proprietary imputation-based marker selection algorithms to maximize the genomic coverage for this array. Reference panels from KGP and European ancestry populations coupled with advanced imputation algorithms provide improved genomic coverage over the commonly used pair-wise tagging methods alone. Imputed markers of interest can be checked here http://www.ukbiobank.ac.uk/axiom-array-query-form/
Imputation reference panel 1000 Genomes Phase 3: UK10K haplotype reference panel was merged together with the 1000 Genomes Phase 3 reference panel using the –merge_ref_panels ​option in the IMPUTE2 software. An advantage of this reference panel is that it includes SNPs, short indels and larger structural variants. The reference panel consists of 87,696,888 bi-allelic variants in 12,570 haplotypes.
ExomeChip versions Affymetrix Axiom
N Whole genome sequenced No
N APOE genotyped Controls N
Controls N: Target 500,000
Platform: UK Biobank Axiom® Array
Comments: Alzheimer’s disease and ApoE markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. Additionally, a dense set of markers spanning the ApoE region are included on this array, including two SNPs, rs429358 and rs7412, which define the ApoE isoforms known to be associated with risk of Alzheimer’s disease and other conditions. Both of these SNPs are previously unavailable on any microarray product.
N not APOE genotyped Controls N
Controls N: 0
Gene screening
APOE Yes
Estimated N: N=500,000.
TREM2 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
APP Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PSEN1 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PSEN2 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
GRN Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
MAPT Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
C9ORF72 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
VCP Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
CHMP2B Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
TDP-43 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PRNP Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
SNCA Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
LRRK2 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PINK1 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PARK2 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
PARK7 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
NOTCH3 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
CST3 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
TTR Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
GSN Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
ITM2B Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
HTT Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
NPC1 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/
NPC2 Yes
Estimated N: N=500,000. This gene has some markers included the array. Alzheimer’s disease markers in these categories were chosen from a list of variants showing some evidence of association with Alzheimer’s disease from meta-analysis of Alzheimer’s association studies and a set of mitochondrial markers suspected to be associated with the disease from an Alzheimer’s disease research group. See DataShowcase for SNPs: http://biobank.ctsu.ox.ac.uk/crystal/

Biological samples

Variable Response
Blood collected Yes
Plasma Yes
Serum Yes
RNA Yes
DNA Yes
Abeta 1-40 No
Abeta 1-42 No
Abeta x-40 No
Abeta x-42 No
Blood Metabolic Analytes
CRP (c-reactive protein) Yes
Comments: Serum- Beckman Coulter, AU5400, Immunoturbidimetric- high sensitivity
eGFR (estimated Glomular Filtration Rate) Yes
Comments: Can be derived from other collected variables.
Glucose Yes
Comments: Serum, Beckman Coulter- AU5400, Hexokinase.
HbA1c Yes
Comments: Red blood cells, Bio-Rad, VARIANT II Turbo, HPLC.
Lipids Yes
Comments: Lipoprotein (a) and Directo Low Density Lipoprotein
Liver Function Tests Yes
Serum creatinine Yes
Comments: Enzymatic creatinine, Serum, Beckman Coulter, AU5400.Analysis: Enzymatic (creatinase).
Homocysteine No
Folate No
Other blood samples Yes
Are laboratory protocols and storage information available for bloods Yes
Urine collection
Urine Yes
Details: Sodium (Beckman Coulter), potassium (Beckman Coulter, ISE), microalbumin (Randox, immunoturbidimetric), enzymatic creatinine (Beckman Coulter). For protocols for urine collection, see Elliott et al. ( 2008).
Autopsy data
Autopsy No
Measurements already performed No
Saliva
Saliva collected Yes
Subgroup
Repeated Collection: Repeated at reassessment visits
Cortisol No
Are laboratory protocols and saliva storage information available? Yes
CSF
CSF collected No
Are CSF laboratory protocols and storage information available? No
Mitochondrial function Data available: MItochondrial genetics have been included in the genetics work.
mtDNA abnormalities Yes
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? Yes
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
Comments: Alcohol
Specified beverage type (wine, spirits, beers) Data available: Including size of drink, whether or not with meals
Abstainers/former users Data available
Binge drinking Data available
Drugs of abuse assessment
Obesity and associated risk factors
BMI Data available
Hip/waist circumference Data available
Fat percentage Data available
Dyslipidemia Data available
Blood lipids Data available
Metabolic syndrome Data available
Type of exercise: heavy, light Data available
Exercise duration Data available
Occupation possible job matrices Data available: Assessment of activity involved in job
Objective measures of activity Data available
Comments: Activity monitors sent out by mail to 100,000 participants.
Objective measure of fitness (VO2) Data available: Treadmill assessed: This category contains data on cardio-respiratory fitness, and involves heart-rate monitoring (using a 4-lead electrocardiograph ECG, CAM-USB 6.5, Cardiosoft v6.51) during cycle ergometry on a stationary bike (eBike, Firmware v1.7) with a ramp slope that is adapted to the individual based on age, gender, weight and medical history. ECGs were recorded pre-test (15 seconds), during activity (6 minutes) and in recovery (1 minute). The participant's risk category was first calculated to determine what level of activity they should perform or have only a resting ECG performed. The percentage levels of effort during activity were then determined according to their risk category, and their maximum workload was calculated according to age, height, weight, resting heart rate and sex. These measures were introduced to the Assessment Centre towards the end of recruitment.
Other measurements of activity Activity monitors sent out by mail.
Diet Yes
Carbs, protein, fats, fish oil Data available
Anti-oxidants Data available
Vegetarian? Data available
Shortage of food Data available
Coffee and caffeine Data available
Vitamin A, B, E Data available
Fat intake MUFA, PUFA Data available
Food questionnaires Data available
Other dietary items Yes
Employment status
Employment status Data available
Comments: Comprehensive assessment of type of work, length in employment etc.
Living situation
Living situation Data available
Socioeconomic status
Socioeconomic status measures Data available
Sleep assessment
Questionnaires Data available
Comments: Sleep duration, getting up in the morning, chrontype, nap during day, sleeplessness, snoring, daytime sleeping (narcolepsy)
Actigraphy to measure sleep patterns Data available

Ethics and Engagement

Variable Response
Participant engagement
Is there participant representation in the governance of the cohort? No
Ethics
Is there an ethics advisory or ELSI group within the cohort governance? The UK Biobank Ethics and Governance Council (EGC) is an independent committee established by the Wellcome Trust and the Medical Research Council. Its purposes are:
To act as an independent guardian of the UK Biobank Ethics and Governance Framework (EGF) and advise on its revision,
To monitor and report publicly on the conformity of the UK Biobank project with the EGF,
To advise more generally on the interests of research participants and the general public in relation to UK Biobank. The Ethics and Governance Framework (EGF) sets standards for the UK Biobank project so that all necessary safeguards are in place to ensure that the data and samples are only used for scientifically and ethically approved research. The first public draft of the Ethics and Governance Framework (EGF) was developed with the advice of an Interim Advisory Group which met three times between February and July 2003. The group included experts in research ethics, philosophy, law, science and social science, and consumer representation, and was chaired by Dr William Lowrance, a consultant in health policy and ethics. The document went out to public consultation. A revised draft EGF was developed by UK Biobank in 2006, and agreed by the Board and the EGC. The EGF is expected to evolve through the course of the UK Biobank project, adapting to scientific, ethical, legal and other developments.
If yes, who is represented on it? Chaired by Prof Sir Michael Rawlins. All of these people are external.
Does the cohort include participants who lack capacity? No
Is there a process in place for participants who lose capacity? Yes
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) At the initial assessment visit: It would be impractical and inappropriate to conceal 
from participants some  of the  measurements taken in  their enrolment visit (i.e.
blood  pressure,  height, weight, estimated  amount of fat). Consequently, a  printed 
report will  be  provided  at the  end  of their visit as a  means of feeding  back such 
measurements. By reporting  standard  ranges, the  participant should be  provided 
with sufficient information to give meaning to the measurements taken, so that they 
may act on the results if necessary and arrange to see their general practitioner or
other relevant health professional.
UK Biobank is working with social scientists and health economists to gain a better understanding of the risks and benefits associated with providing feedback of potentially serious incidental findings to UK Biobank participants during the imaging pilot study. In some cases, these incidental findings can have serious health implications, in others, the medical implications are less clear, and many potentially serious findings may – after further investigation or the passage of time – turn out not to be of concern after all. The impact that feedback of information about potentially serious incidental findings has on participants has not been well researched. This work is important because there is currently no consensus in the research community on which (if any) incidental findings should be fed back and the best methods for doing this. The UK Biobank imaging pilot study offers a valuable opportunity to ascertain the views of research participants and of health professionals involved in the feedback process, including radiographers, radiologists and GPs.
The work has four key aims:: 1. To assess the attitudes of participants to receiving feedback of potentially serious incidental findings and to understand whether these attitudes change over time.
2. To understand the impact of receiving feedback on UK Biobank participants and on their friends and families.
3. To assess the attitudes of radiographers, radiologists and GPs (who are involved in the feedback process) to the procedures established by UK Biobank for the feedback of incidental findings during the imaging pilot study.
4. To help inform the policy on feedback for the main phase of the imaging study.
This research will involve sending out questionnaires to assess the impact of receiving information about a potentially serious incidental finding to participants and their GPs. Qualitative research will also be conducted based on interviews with participants and health professionals (GPs, radiographers and radiologists). The results will be used to inform the main phase of the imaging study.
Who is responsible for disclosing incidental findings? Radiologist.
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)? UK Biobank sought to recruit as widely generalisable  a  population sample  as is
practicable so that the research may ultimately benefit a wide diversity of people. UK 
Biobank sought to reduce  barriers to participation (such as those relating  to age, gender, ethnicity, social class, residence, employment, and  language) through, among 
other things, the location and opening times of assessment centres and by translation of
study materials.
UK Biobank identified potential participants from contact  details in  NHS  records
(and other registers), without access to any medical information. These contact details
are processed in confidence by UK Biobank, in accordance with the Data Protection 
Act. Potential participants are sent information about the study and invited to 
attend a local UK Biobank Assessment CentreCentral repository of health information.
Does the study involve ongoing connections with participants' own doctors (e.g. GPs)? No
Consent and recontact
Is there consent for recontact? Yes
If so, under what conditions? Researchers are able to request re-contact of participants as part of their Application. Proposals for re-contact are subject to careful review to ensure that the re-contact is justifiable and will not over-burden participants or reveal health information.

Data Management

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