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DISCUSSION BIOST/EPI 536

DISCUSSION BIOST/EPI 536. Tuesday, December 8, 2009. Outline. Review of genetic terminology Weekly quiz Interpretation of regression coefficients (HW 14). Genetic terms. Allele 1. Homologous pair of chromosomes. Locus. Allele 2.

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DISCUSSION BIOST/EPI 536

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  1. DISCUSSIONBIOST/EPI 536 Tuesday, December 8, 2009

  2. Outline • Review of genetic terminology • Weekly quiz • Interpretation of regression coefficients (HW 14)

  3. Genetic terms Allele 1 Homologous pair of chromosomes Locus Allele 2 • Genotype: A pair of alleles located at a specific location on homologous chromosomes, whose expression contributes to some observed trait • -- Homozygous: Same alleles (e.g., AA) • -- Heterozygous: Different alleles (e.g., Aa) One allele inherited from each parent

  4. Genetic terms Genotype aa Bb DD SNP 1 SNP 2 SNP 3 a B D a b D Haplotypes: (a,B,D) (a,b,D) Diplotype • Haplotype: A combination of alleles at multiple loci that are inherited together on the same chromosome • Diplotype: A pair of haplotypes from homologous chromosomes

  5. Genotype aa Bb DD Genotype 0 1 2 SNP 1 SNP 2 SNP 3 SNP 1 SNP 2 SNP 3 a B D 0 1 1 a b D 0 0 1 Haplotypes: (a,B,D) (a,b,D) Haplotypes: (0,1,1) (0,0,1) Diplotype Diplotype Counting alleles denoted in capital letters as those of interest…

  6. Week 10 Quiz • Dr. Austin was interested in whether genotype at a genetic locus on chromosome 4 was related to the risk of myocardial infarction. She conducted a case-control study among 60-65 year old men in the Seattle area. • Subject ascertainment methods were unbiased. • The study was adequately powered. • There was no matching. • At the genetic locus in question, one of five alleles exist: • A, B, C, D, and E.

  7. Week 10 Quiz She fit the following logistic model: logit p = -1.02 + 0.48xB + 0.54xC + 0.51xD + 0.52xE xB = # of B alleles in a subject’s genotype xC = # of C alleles in a subject’s genotype xD = # of D alleles in a subject’s genotype xE = # of E alleles in a subject’s genotype Based on the results of this model, one of Dr. Austin’s students concluded that each additional copy of allele B causes an increase in risk of MI among 60-65 year old men. Is this a correct interpretation? Why or why not?

  8. Week 10 Quiz Model: logit p = α + βBxB + βCxC + βDxD + βExE Consider the log odds of MI for each genotype Allele 2 Genotype comparisons for which log OR = βB?

  9. HW 14: Model A Letting xi = 1 if the haplotype is present, and 0 otherwise for i = 2, 3, or 4: logit p = α + β2x2 + β3x3 + β4x4 What is the interpretation of β2?

  10. HW 14: Model A Model A: logit p = α + β2x2 + β3x3 + β4x4 Consider the log odds of being a case for each diplotype 2nd Haplotype Diplotype comparisons for which log OR = β2?

  11. HW 14: Model B Letting xi = the number of ith haplotypes present in a subject’s diplotype (0, 1, 2) for i = 2, 3, or 4: logit p = α + β2x2 + β3x3 + β4x4 What is the interpretation of β2?

  12. HW 14: Model B Model B: logit p = α + β2x2 + β3x3 + β4x4 Consider the log odds of being a case for each diplotype 2nd Haplotype Diplotype comparisons for which log OR = β2?

  13. HW 14: Model C Letting diplotype 1 be the reference haplotype, and xi=1 if the ith diplotype is present and 0 otherwise for i = 2,…,10: logit p = α + β2x2 + … + β10x10 What is the interpretation of β4, β5, β8, and β9?

  14. HW 14: Differences in models • What constraints are imposed by each model? • Model A: • Model B: • Model C: • Are any of these reparameterizations of one another?

  15. HW 14: Differences in models How does the interpretation of β2 in models A and B differ? Is the interpretation of β2 in these two models comparable to the interpretation of β4, β5, β8, or β9 in model C?

  16. Revisiting some general principles • The interpretation of a regression coefficient depends on what other variables are included in the model. • The interpretation of a regression coefficient depends on how variables are coded in the model.

  17. Questions?

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