Z-score在GWAS summary statistics中的含义是什么？

The Z-score quantifies how many standard deviations an observed association statistic is from the expected null distribution under the assumption of no association.

1. Association Testing: In a GWAS, genetic variants across the genome are tested for their association with a particular trait or disease. The most common statistical test used for this purpose is logistic regression for binary traits (e.g., disease status) or linear regression for continuous traits (e.g., height).

2. Z-Score Calculation: After performing the association test for each SNP, a Z-score is calculated for that SNP. The formula for calculating the Z-score is typically as follows:

   Z = (β - β₀) / SE
   

   • Z is the Z-score.
   • β is the estimated effect size or regression coefficient for the SNP, representing the change in the trait value associated with each additional copy of the variant.
   • β₀ is the null hypothesis value for β, often assumed to be zero under the null hypothesis of no association.
   • SE is the standard error of the estimated effect size β.

3. Interpretation: The Z-score measures how many standard deviations (SE) the estimated effect size (β) is away from the null hypothesis value (β₀). A high absolute Z-score indicates a strong association between the SNP and the trait, whereas a low or close-to-zero Z-score suggests a weak or no association.

4. Significance Threshold: Researchers typically establish a significance threshold (e.g., Z-score greater than 5 or corresponding p-value threshold) to determine which associations are statistically significant. Associations with Z-scores exceeding this threshold are considered noteworthy and may indicate a genuine genetic influence on the trait or disease.

5. Positive and Negative Z-Scores: The sign of the Z-score indicates the direction of the effect. A positive Z-score suggests that the variant is positively associated with an increase in the trait (e.g., risk allele for a disease). A negative Z-score suggests a negative association (e.g., protective allele for a disease).