Guidelines for Human Phenotype-Genotype Association Studies

Last Updated: December 12, 2024

SECTION 1: GENERAL PRINCIPLES
===========================

1. Study Design Requirements
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□ Essential elements:
- Clear hypothesis statement
- Power calculation justification
- Sample size determination
- Population stratification consideration
- Control selection criteria
- Replication strategy

2. Ethical Considerations
---------------------
□ Mandatory requirements:
- IRB/Ethics committee approval
- Informed consent documentation
- Data privacy protection
- Genetic counseling provisions
- Return of results policy
- Biobank compliance (if applicable)

SECTION 2: PHENOTYPE CHARACTERIZATION
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1. Phenotype Definition
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□ Required documentation:
- Detailed phenotype description
- Standardized terminology use
- Assessment methods
- Quality control measures
- Phenotype validation
- Environmental factors consideration

2. Data Collection Standards
-----------------------
□ Requirements for:
- Standardized collection methods
- Validated instruments
- Inter-rater reliability
- Missing data handling
- Outlier identification
- Longitudinal tracking (if applicable)

SECTION 3: GENOTYPE ANALYSIS
=========================

1. Sample Collection and Processing
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□ Standards for:
- DNA/RNA extraction methods
- Sample quality control
- Storage conditions
- Chain of custody
- Batch effects monitoring
- Technical replication

2. Genotyping Methods
------------------
□ Requirements:
- Platform description
- Quality metrics
- Call rate thresholds
- Hardy-Weinberg equilibrium testing
- Minor allele frequency reporting
- Variant annotation standards

SECTION 4: STATISTICAL ANALYSIS
===========================

1. Primary Analysis
---------------
□ Required elements:
- Association test methods
- Multiple testing correction
- Population stratification control
- Effect size estimation
- Confidence interval calculation
- Power analysis results

2. Secondary Analyses
-----------------
□ Guidelines for:
- Subgroup analyses
- Interaction testing
- Pathway analysis
- Functional prediction
- Meta-analysis
- Replication studies

SECTION 5: DATA SHARING AND REPORTING
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1. Data Deposition
---------------
□ Requirements for:
- Raw data submission
- Metadata documentation
- Approved repositories
- Access controls
- Version control
- Data retention period

2. Results Reporting
----------------
□ Standards for:
- Effect size reporting
- P-value presentation
- Forest plots
- Manhattan plots
- Q-Q plots
- Regional association plots

SECTION 6: QUALITY CONTROL
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1. Laboratory QC
------------
□ Requirements:
- Sample tracking
- Contamination prevention
- Batch effect monitoring
- Control sample inclusion
- Technical replication
- Standard operating procedures

2. Data QC
--------
□ Standards for:
- Genotype calling
- Missing data handling
- Relatedness testing
- Sex verification
- Ancestry estimation
- Batch effect correction

SECTION 7: REPRODUCIBILITY
=======================

1. Documentation Requirements
------------------------
□ Must include:
- Analysis scripts
- Software versions
- Parameter settings
- Reference genome version
- Annotation databases
- Pipeline documentation

2. Validation Studies
-----------------
□ Guidelines for:
- Independent replication
- Cross-population validation
- Functional validation
- Clinical correlation
- Meta-analysis inclusion

SECTION 8: SPECIAL CONSIDERATIONS
=============================

1. Rare Variants
------------
□ Guidelines for:
- Variant calling
- Frequency estimation
- Functional prediction
- Segregation analysis
- Family studies
- Population-specific considerations

2. Complex Traits
-------------
□ Requirements for:
- Heritability estimation
- Genetic architecture
- Pleiotropy analysis
- Gene-environment interactions
- Phenotype decomposition

APPENDIX A: SUBMISSION CHECKLIST
============================

Required Documentation
--------------------
□ Must include:
- Study protocol
- Ethics approval
- Data sharing statement
- STROBE-G checklist
- Quality metrics report
- Analysis scripts

Note: These guidelines align with COPE standards, NIH Genomic Data Sharing Policy,
and International Committee of Medical Journal Editors (ICMJE) requirements.