Figure 4

Extreme phenotypes for case–reference association studies in the European Cystic Fibrosis Twin and Sibling Study (ECFTSS). a) Definition of the composite parameter based on rank numbers for weight-for-height (WfH) % predicted and cystic fibrosis (CF) disease centiles for forced expiratory volume in 1 s % predicted (FEVPerc) [15]. Rank numbers were assigned for the entire study population of ECFTSS (318 pairs, individual patients ranked 1–636) and the most extreme phenotypes were selected for the association study based on delta and distance from origin. Note that the composite parameter delta is significantly lower for monozygous than for dizygous twins, while intrapair differences for WfH % predicted and FEVPerc are indistinguishable by zygosity. In other words, the composite parameter delta is more sensitive towards an inherited component than the individual parameters from which it is derived. b) Three examples of the same diagram for the extreme phenotypes. Con+: concordant mildly affected; Con-: concordant severely affected; Dis: discordant.