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Biostatistics Correlation and linear regression Burkhardt Seifert & Alois Tschopp Biostatistics Unit University of Zurich Master of Science in Medical Biology 1 Correlation and linear regression Analysis of the relation of two continuous


  1. Biostatistics Correlation and linear regression Burkhardt Seifert & Alois Tschopp Biostatistics Unit University of Zurich Master of Science in Medical Biology 1

  2. Correlation and linear regression Analysis of the relation of two continuous variables (bivariate data). Description of a non-deterministic relation between two continuous variables. Problems: 1 How are two variables x and y related? (a) Relation of weight to height (b) Relation between body fat and bmi 2 Can variable y be predicted by means of variable x ? Master of Science in Medical Biology 2

  3. Example Proportion of body fat modelled by age, weight, height, bmi, waist circumference, biceps circumference, wrist circumference, total k = 7 explanatory variables. Body fat: Measure for “health”, measured by “weighing under water” (complicated). Goal: Predict body fat by means of quantities that are easier to measure. n = 241 males aged between 22 and 81. 11 observations of the original data set are omitted: “outliers”. Penrose, K., Nelson, A. and Fisher, A. (1985), “Generalized Body Composition Prediction Equation for Men Using Simple Measurement Techniques”. Medicine and Science in Sports and Exercise, 17 (2), 189. Master of Science in Medical Biology 3

  4. Bivariate data Observation of two continuous variables ( x , y ) for the same observation unit − → pairwise observations ( x 1 , y 1 ) , ( x 2 , y 2 ) , . . . , ( x n , y n ) Example: Relation between weight and height for 241 men Every correlation or regression analysis should begin with a scatterplot 110 ● ● ● ● ● ● ● ● ● ● 100 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 90 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● weight ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 80 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 70 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 60 ● ● ● ● ● ● ● ● ● ● 160 170 180 190 200 height − → visual impression of a relation Master of Science in Medical Biology 4

  5. Correlation Pearson’s product-moment correlation measures the strength of the linear relation, the linear coincidence, between x and y . n 1 � Covariance: Cov( x , y ) = s xy = ( x i − ¯ x )( y i − ¯ y ) n − 1 i =1 n 1 � s 2 x ) 2 Variances: ( x i − ¯ x = n − 1 i =1 n 1 � s 2 y ) 2 y = ( y i − ¯ n − 1 i =1 � ( x i − ¯ x )( y i − ¯ y ) r = s xy Correlation: = �� x ) 2 � s x s y y ) 2 ( x i − ¯ ( y i − ¯ Master of Science in Medical Biology 5

  6. Correlation Plausibility of the enumerator: � ( x i − ¯ x )( y i − ¯ y ) r = s xy Correlation: = �� x ) 2 � s x s y y ) 2 ( x i − ¯ ( y i − ¯ − + + + − − − + + − Plausibility of the denominator: r is independent of the measuring unit. Master of Science in Medical Biology 6

  7. Correlation Properties: − 1 ≤ r ≤ 1 r = 1 → deterministic positive linear relation between x and y r = − 1 → deterministic negative linear relation between x and y r = 0 → no linear relation In general: Sign indicates direction of the relation Size indicates intensity of the relation Master of Science in Medical Biology 7

  8. Correlation Examples: r=1 r=−1 r=0 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● y ●● y y ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● x x x r=0 r=0.5 r=0.9 ● ● ● ● ● ●● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● ●● ● ● ● ● ● ● ● ● ● ● y y y ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● x x x Master of Science in Medical Biology 8

  9. Correlation Example: Relation between blood serum content of Ferritin and bone marrow content of iron. 4 ● r = 0 . 72 ● ● ● ● ● ● bone marrow iron 3 ● ● ● ● ● ● ● ● ● ● ● Transformation to linear relation? 2 ● ● ● ● ● ● ● ● 1 Frequently a transformation to the ● ● ● ● ● ● ● normal distribution helps. 0 ● ● ●● ● ● ● ● ● ● ● 0 100 200 300 400 500 600 serum ferritin 4 ● ● ● ● ● ● ● bone marrow iron 3 ● ● ● ● ● ● ● ● ● ● ● r = 0 . 85 2 ● ● ● ● ● ● ● ● 1 ● ● ● ● ● ● ● 0 ● ● ● ● ● ● ● ● ● ● ● 0 1 2 3 4 5 6 7 log of serum ferritin Master of Science in Medical Biology 9

  10. Tests on linear relation Exists a linear relation that is not caused by chance? Scientific hypothesis: true correlation ρ � = 0 Null hypothesis: true correlation ρ = 0 Assumptions: ( x , y ) jointly normally distributed pairs independent � n − 2 Test quantity: T = r 1 − r 2 ∼ t n − 2 Master of Science in Medical Biology 10

  11. Tests on linear relation Example: Relation of weight and body height for males. n = 241 , r = 0 . 55 − → T = 7 . 9 > t 239 , 0 . 975 = 1 . 97 , p < 0 . 0001 Confidence interval: Uses the so called Fisher’s z -transformation leading to the approximative normal distribution ρ ∈ (0 . 46 , 0 . 64) with probability 1 − α = 0 . 95 Master of Science in Medical Biology 11

  12. Spearman’s rank correlation Treatment of outliers? Testing without normal distribution? ● 160 140 120 ● weight ● ● ● ● ● ● ● 100 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 80 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 60 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● 60 80 100 120 140 160 180 200 height n = 252 , r = 0 . 31 , p < 0 . 0001 Master of Science in Medical Biology 12

  13. Spearman’s rank correlation Idea: Similar to the Mann-Whitney test with ranks Procedure: 1 Order x 1 , . . . , x n and y 1 , . . . , y n separately by ranks 2 Compute the correlation for the ranks instead of for the observations − → r s = 0 . 52 , p < 0 . 0001 (correct data ( n = 241) : r s = 0 . 55 , p < 0 . 0001) Master of Science in Medical Biology 13

  14. Dangers when computing correlation 1 10 variables → 45 possible correlations (problem of multiple testing) ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Nb of variables 2 3 5 10 Nb of correlations 1 3 10 45 P(wrong signif.) 0.05 0.14 0.40 0.91 Number of pairs increases rapidly with the number of variables. − → increased probability of wrong significance 2 Spurious correlation across time (common trend) Example: Correlation of petrol price and divorce rate! 3 Extreme data points: outlier, “leverage points” Master of Science in Medical Biology 14

  15. ✂ ✁ � Dangers when computing correlation ● ● ● ● ● ● ● 4 Heterogeneity correlation ● ● ● (no or even opposed relation y + + within the groups) + + + + + + + + x 5 Confounding by a third variable Example: Number of storks and births in a district − → confounder variable: district size 80 6 Non-linear relations (strong 60 (x-10.5)^2 relation, but r = 0 − → not 40 meaningful) 20 0 5 10 15 20 x Master of Science in Medical Biology 15

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