Table 1 Data sources for main analyses.

From: Genetically modeled GLP1R and GIPR agonism reduce binge drinking and alcohol-associated phenotypes: a multi-ancestry drug-target Mendelian randomization study

Category

Consortium / Project

Trait Assessed

Sample Size

N Cases

N Controls

Units

GLP1R and GIPR Instrumentation

 Primary instruments

UK Biobank and GIANT

Body Mass Index (BMI)

694,349

NA

NA

Kilograms (kg)/m2

Neale Lab / UK Biobank

Glycated Hemoglobin (HbA1c)

344,132

NA

NA

% (to)

 Data for replication

Million Veterans Program (MVP)

BMI

424,221

NA

NA

kg/m2

HbA1c

338,848

NA

NA

% (mmol/mol)

 

MetaBrain Consortium

GLP1R and GIPR Brain Expression (Cortex)

2,683

NA

NA

Gene Expression Level

Liver Health

 

FinnGen Data Freeze 11 (DF11)

Alcohol-related Liver Disease (ALD)

443,631

3,330

440,301

Cases/Controls

 

UK Biobank

Non-Alcoholic Fatty Liver Disease (NAFLD) + Liver Fat (MTAG GWAS)

778,614

8,434

770,180

% Liver Fat

 

Alanine Aminotransferase (ALT) Levels

389,733

NA

NA

U/L

 

Alkaline Phosphatase (ALP) Levels

389,733

NA

NA

U/L

 

Gamma-Glutamyl Transpeptidase (GGT) Levels

344,104

NA

NA

U/L

 

Aspartate Aminotransferase (AST) Levels

436,275

NA

NA

U/L

Substance Use Behaviors

 

Psychiatric Genetics Consortium (PGC)

Tobacco Use Disorder (TUD)

739,895

174,021

565,874

Cases/Controls

 

Problematic Alcohol Use (PAU)

468,869

NA

NA

Cases/Controls

 

Cannabis Use Disorder (CUD)

886,025

42,281

843,744

Cases/Controls

 

Opioid Use Disorder (OUD)

554,186

15,251

538,935

Cases/Controls

 

GSCAN

Alcoholic Drinks Per Week

666,978

NA

NA

Drinks/Week

 

Neale Lab / UK Biobank

Frequency of Consuming 6 Alcoholic Drinks per Occasion

143,658

NA

NA

Categorical

 

Complex Traits Genetics Lab

Internalizing vs. Low Risk (2v1)

210,678

109,542

101,136

Cases/Controls

 

Heavy Drinking vs. Low Risk (3v1)

193,564

92,428

101,136

 

Broad Risk vs. Low Risk (4v1)

185,043

83,907

101,136

 

Heavy Drinking vs. Internalizing (3v2)

201,970

92,428

109,542

 

Broad Risk vs. Internalizing (4v2)

193,449

83,907

109,542

 

Broad Risk vs. Heavy Drinking (4v3)

176,335

83,907

92,428

Food Liking

  

Food Liking Scores

159,527

NA

NA

Score

Positive Controls

 

DIAGRAM

Type 2 Diabetes (T2D)

1,812,013

242,283

1,569,730

Cases/Controls

 

FinnGen DF11

Obesity

453,522

27,711

425,881

Cases/Controls

 

Extreme Obesity

427,311

1,289

426,022

Cases/Controls

  1. The table summarizes data sources used in the analysis of GLP1R and GIPR agonism on metabolic health, substance use, binge drinking, liver-related outcomes, and food preferences for the main analyses in populations of European ancestry (sample sizes reflect the main European GWAS). The Million Veteran Program (MVP) provides independent replication datasets for BMI (measured in kg/m²) and HbA1c (measured as a percentage, reflecting mmol/mol), complementing UK Biobank and Neale Lab data. Liver health outcomes, including Non-Alcoholic Fatty Liver Disease (NAFLD) assessed as liver fat percentage, as well as liver enzymes—alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) measured in U/L—were obtained from UK Biobank and FinnGen. Alcohol-related Liver Disease (ALD) was assessed using case-control data from FinnGen DF11, the latest release incorporating improved quality control. Substance use behaviors were assessed using data from the Psychiatric Genetics Consortium (PGC) for Problematic Alcohol Use (PAU), Tobacco Use Disorder (TUD), Cannabis Use Disorder (CUD), and Opioid Use Disorder (OUD). Alcohol consumption traits were derived from GSCAN, the GWAS & Sequencing Consortium of Alcohol and Nicotine Use. Binge drinking frequency was assessed with the question, “How often do you have six or more drinks on one occasion?” with responses categorized as Prefer not to answer, Never, Less than monthly, Monthly, Weekly, and Daily or almost daily. Alcohol misuse classifications were based on latent class analysis (LCA) in UK Biobank, grouping individuals into six pairwise comparisons of drinking patterns and psychiatric comorbidities. Food liking scores were assessed through UK Biobank dietary questionnaires, capturing genetic influences on preferences for specific food categories. Positive control outcomes include Type 2 Diabetes (T2D) from DIAGRAM and obesity-related traits from FinnGen DF11. See Table S1 for full data source information and links to the data repositories.
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