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Heterogeneity Testing

Heterogeneity Testing. Elizabeth Prom-Wormley and Hermine Maes. Heterogeneity Questions . Univariate Analysis: What are the contributions of additive genetic, dominance/shared environmental and unique environmental factors to the variance ? Heterogeneity:

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Heterogeneity Testing

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  1. Heterogeneity Testing Elizabeth Prom-Wormley and HermineMaes

  2. Heterogeneity Questions • Univariate Analysis: • What are the contributions of additive genetic, dominance/shared environmental and unique environmental factors to the variance? • Heterogeneity: • Are the contributions of genetic and environmental factors equal for different groups, • sex, race, ethnicity, SES, environmental exposure, etc.?

  3. Getting a Feel for the Data • Gentlemen- Open ACEm.R • Ladies- Open ACEf.R • Zygosity Coding • MZF = 6 • DZF = 8 • MZM = 7 • DZM = 9 • Opp Sex = 10 • First Steps?

  4. Getting a Feel for the Data

  5. What’s the Question?Qualitative Differences • Are the differences due to differences in the source/nature of the effects (qualitative)? • Are there different genetic/environmental factors influencing the trait in males and females?

  6. Classic Univariate ACE Model MZ = 1 / DZ = 0.5 1 C A A C E E a c e a c e T1 T2

  7. Classic Univariate ACE Model + Qualitative Sex Differences MZ = 1 / DZ = 0.5 MZ = 1 / DZ = 0.5 1 1 Am Af am af cf cm ef em Cf Cm Am Af Cf Cm Em Ef Em Ef af am cf cm ef em Male Model T1 T1 T2 T2 Female Model

  8. Testing Qualitative Differences • Non-Scalar limitation • Without opposite sex twin pairs (Qualitative) • Male Parameters • meansM • AM CM and EM • Female Parameters • meanF • AF CF and EF • Parameters are estimated separately • varMale≠ varFemale • AMale≠ AFemale • CMale≠ CFemale • EMale≠ EFemale

  9. Conclusions from Qualitative Modeling?Limitations of Qualitative Modeling?

  10. Getting a Feel for the Data

  11. What’s the Question?Quantitative Differences • Are these differences due to differences in the magnitude of the effects (quantitative)? • Is the contribution of genetic/environmental factors greater/smaller in males than in females? • Test Models of Scalar and Non-Scalar Influences

  12. Classic Univariate ACE ModelNo Heterogeneity MZ = 1 / DZ = 0.5 1 C A A C E E a c e a c e T1 T2

  13. Classic Univariate ACE Model + Scalar Sex Limitation on the Variance MZ = 1 / DZ = 0.5 1 C A A C E E k*a k*c k*e a c e T1F T2M

  14. Scalar limitation (Quantitative) • Proportion of variance due to A,C,E are the same between groups • The total variance is not ie: • varFemale= k*varMale • AFemale= k*AMale • CFemale= k*CMale • EFemale= k*EMale

  15. Quantitative DifferencesNon-Scalar Limitation • With opposite sex twin pairs (Quantitative) • Male Parameters • meansM • AM CM and EM • Female Parameters • meanF • AF CF and EF • Parameters are estimated jointly – linked via the opposite sex correlations • r(AFemale ,Amale) = .5 • r(CFemale≠ CMale ) = 1 • r(EFemale≠ EMale ) = 0

  16. Classic Univariate ACE Model + Non-Scalar Sex Limitation rODZ= 0.5 1 Am af cf ef Cm Cf Af Ef Em am cm em T2M T1F

  17. General Non-Scalar limitation via rG • With opposite sex twin pairs (semi-Qualitative) • Male Parameters • meansM • AM CM EM • Female Parameters • meanF • AF CF and EF • Parameters are estimated jointly – linked via the opposite sex correlations • r(AFemale ,Amale) = ? (estimated) • r(CFemale≠ CMale ) = 1 • r(EFemale≠ EMale ) = 0

  18. Classic Univariate ACE Model + General Non-Scalar Limitation via rG rODZ= ?? 1 Am af cf ef Cm Cf Af Ef Em am cm em T2M T1F

  19. Open twinHet5AceCon.R

  20. General Non-Scalar limitation • With opposite sex twin pairs (semi-Qualitative) • Male Parameters • meansM • AM CM EM and ASpecific • Extra genetic/ environmental effects • Female Parameters • meanF • AF CF and EF Parameters are estimated jointly – linked via the opposite sex correlations

  21. Classic Univariate ACE Model + General Non-Scalar Sex Limitation rODZ= 0.5/1 1 Am af cf ef Cm Cf Af Ef Em am cm em As T2M T1F as

  22. Open alt_twinHet5AceCon.R

  23. So How Important is Sex-Limitation Working?

  24. Review- Heterogeneity Questions • Quantitative- Are these differences due to differences in the magnitude of the effects? • Is the contribution of genetic/environmental factors greater/smaller in males than in females? • Qualitative- Are the differences due to differences in the source/nature of the effects? • Are there different genetic/environmental factors influencing the trait in males and females?

  25. Review- The language of heterogeneity

  26. Heterogeneity Terminology • Depends on research question • Moderation, confounding, interaction (or GxE) • Systematic differences • Measured or manifest moderator/confounder • Unmeasured (latent) moderator/confounder

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