SMAD3 and Alzheimer disease: Other complex diseases that have high-risk scores are diabetes mellitus,35 rheumatoid arthritis, and Alzheimer’s disease.36 The top ten genes that have the highest risk score sum of all eleven age-related complex diseases are PPARG, IGFBP7, TGFBR1, PSEN1, B3GLCT, APP, APOC1, APOE, VEGFA, and SMAD3 (Fig. 5d).