Text S2: References for disease frequency and heritability

Citations to papers providing lifetime morbid risks and heritabilities, and proportions of heritability explained are provided in Tables S6 and S7. Where multiple values for heritability are shown in Table S7, we used an inverse variance weighted average to obtain the value shown in Table 2. For age-related macular degeneration (AMD), celiac disease, Crohn disease, and ulcerative colitis, the values of lifetime morbid risk were estimated based on available incidence data. Incidence rates for late AMD (i.e., geographic atrophy or neovascular AMD) were based on the Rotterdam Study [1]. In the case of celiac disease, a constant incidence rate of 9.1 cases per 100,000 individuals per year was assumed [2]. Incidence numbers for Crohn disease and ulcerative colitis were taken from a recent study of inflammatory bowel disease rates in a Northern California managed care organization [3]. To model competing risks, we used overall United States mortality rates [4]. Let it and mt denote the incidence and mortality rates at age t, let pt denote the probability of developing the disease before age t, and let qt denote the probability of surviving to age t without developing the disease or dying from other causes. Then,