Adjustment for index event bias in genome-wide association studies of subsequent events

• DOI: 10.1038/s41467-019-09381-w
• Publication Date: 2019-04-05T10:02:56Z
• Authors: Frank Dudbridge; Richard J. Allen; Nuala A. Sheehan; A. Floriaan Schmidt; James C. Lee; R. Gisli Jenkins; Louise V. Wain; Aroon D. Hingorani; Riyaz S. Patel
• Keywords: Genome-wide Association Study; Genetic Association; Genetic predisposition

Abstract Following numerous genome-wide association studies of disease susceptibility, there is increasing interest in genetic associations with prognosis, survival or other subsequent events. Such are vulnerable to index event bias, by which selection subjects according status creates biased if common causes incidence and prognosis not accounted for. We propose an adjustment for bias using the residuals from regression effects on incidence. Our approach eliminates this when direct independent, otherwise reduces realistic situations. In a study idiopathic pulmonary fibrosis, we reverse paradoxical strong susceptibility gene MUC5B increased survival, suggesting instead significant decreased survival. re-analysis Crohn’s four regions remain associated at significance but standard errors.