Table 1

GWAS datasets used in the study

Phenotypes	Study/dataset	Cohort/consortium	Maximum number of participants	Underlying population	Phenotype assessment	Summary data
Early-life exposure
Education	Okbay et al, 201624 25	64 separate cohorts	293 723	European	Educational attainment was measured by the number of years of schooling completed and assessed in cohorts of participants aged 30 years or above.	Mean=14.3 years (SD=3.6)
Mid-life exposures
Alcohol consumption	Evangelou et al, 201926 27	UK Biobank, Alcohol Genome-Wide Consortium and Cohorts for Heart and Ageing Research in Genomic Epidemiology Plus consortia	480 842	European	Self-reported weekly and monthly alcohol consumption.	Mean=19.8 g of alcohol per day (SD=21.2)
Blood pressure (systolic)	UK Biobank28	UK Biobank	475 142	European	Average of automated readings of systolic blood pressure.	Mean=138.0 mm Hg (SD=19.3)
Age-related hearing loss	Kalra et al, 202029 30	UK Biobank	330 759	European	Self-reported four hearing loss traits1: Do you have difficulty with your hearing?2 Do you find it difficult to follow a conversation if there is background noise (such as TV, radio, children playing)?3 Do you use a hearing aid most of the time?4 Do you get or have you had noises (such as ringing or buzzing in your head or in one or both ears that lasts for more than 5 min at a time?	Trait 1: n=23 333 (4.7%) Trait 2: n=123 089 (37.8%) Trait 3: n=10 322 (5.3%) Trait 4: n=7214 (7.1%)
Obesity	Pulit et al, 201931 32	UK Biobank	694 649	European	Body fat distribution in the form of measurements of waist:hip ratio adjusted for body mass index.	SD=0.0199
Late-life exposures
Depression	Howard et al, 201833 34	UK Biobank	322 580	European	Depression categorised into three groups: Broad depression: measured by self-reported help-seeking behaviour for ‘nerves, anxiety, tension or depression’. Probable major depression: measured by self-reported depressive symptoms with ‘impairment’. Major depression: assessed by hospital admission records.	Broad depression, n=113 769 (35.3%) Probable major depression, n=30 603 (17.5%) Major depression, n=8276 (3.8%)
Diabetes	Scott et al, 201735 36	Diabetes Genetics Replication and Meta-analysis Consortium	159 208	European	Type 2 diabetes assessed based on the prescription medication or laboratory evidence of hyperglycaemia.	Cases, n=26 676 (16.8%)
Loneliness	Day et al, 201837 38	UK Biobank	452 302	European	Self-reported traits: (1) Do you often feel lonely? (2) Composite of: Including yourself, how many people are living together in your household? And: How often do you visit friends or family or have them visit you? (3) How often are able to confide in someone close to you?	Trait 1: n=80 134 (18.0%) Trait 2: n=2426 (0.8%) Trait 3: n=64 505 (21.3%)
Physical activity	Klimentidis et al, 201839 40	UK Biobank	377 234	European	Self-reported activity levels and accelerometer readings.	Vigorous physical activity ≥3 vs 0 days/week, n=98 060 (37.6%)
Smoking	Wootton et al, 201941 42	UK Biobank	462 690	European	Self-reported measures of lifetime smoking including smoking duration, heaviness and cessation.	Mean=0.359, lifetime smoking score SD=0.694
Outcomes
Late-onset AD (clinical diagnosis and family history)	Bellenguez et al, 202215 43	European Alzheimer & Dementia Biobank	788 989	European	Clinical diagnosis of AD plus self-report of at least one first-degree biological relative with a diagnosis of AD.	Cases, n=111 326 (14.1%)
Late-onset AD	Kunkle et al, 201912 44	International Genomics of Alzheimer's Project	94 437	European	Clinical diagnosis or evidenced by autopsy reports.	Cases, n=35 274 (37.4%)
Late-onset AD	Lambert et al, 201313 45	International Genomics of Alzheimer’s Project	74 046	European	Clinical diagnosis or evidenced by autopsy reports.	Cases, n=17 008 (31.4%)
Proxy (family history) risk of AD	Schwartzentruber et al, 202114 46	UK Biobank	408 942	European	Number of first-degree relatives with a diagnosis of AD.	Cases, n=53 042 (13.0%)
DLB	Chia et al, 202147 48	Cohort recruited from various centres across Europe and North America	6618	European	Consensus clinical diagnosis based on established criteria.	Cases, n=2591 (39.2%)
FTD	Ferrari et al, 201449 50	Cohort recruited from 44 international research groups	12 928	European	Consensus clinical diagnosis based on established criteria.	Cases, n=3526 (27.3%)
Post hoc analyses dataset
CAD	Nelson et al, 201710 51	CARDIoGRAMplusC4D Consortium (UK Biobank)	155 197	European	Self-reported angina or other evidence of chronic coronary heart disease including myocardial infarction and/or revascularisation.	Cases, n=17 283 (11.1%)

AD, Alzheimer’s disease; CAD, coronary artery disease; DLB, dementia with Lewy bodies; FTD, frontotemporal dementia; GWAS, genome-wide association study; SD, standard deviation .