To elucidate how variants in genetic risk loci previously implicated in Alzheimer’s Disease (AD) and/or frontotemporal dementia (FTD) contribute to expression of disease phenotypes, a phenome-wide association study was performed in two waves. In the first wave, we explored clinical traits associated with thirteen genetic variants previously reported to be linked to disease risk using both the 23andMe and UKB cohorts. We tested 30 additional AD variants in UKB cohort only in the second wave. APOE variants defining ε2/ε3/ε4 alleles and rs646776 were identified to be significantly associated with metabolic/cardiovascular and longevity traits. APOE variants were also significantly associated with neurological traits. ABI3 variant rs28394864 was significantly associated with cardiovascular (e.g. (hypertension, ischemic heart disease, coronary atherosclerosis, angina) and immune-related trait asthma. Both APOE variants and CLU variant were significantly associated with nearsightedness. HLA- DRB1 variant was associated with diseases with immune-related traits. Additionally, variants from 10+ AD genes (BZRAP1-AS1, ADAMTS4, ADAM10, APH1B, SCIMP, ABI3, SPPL2A, ZNF232, GRN, CD2AP, and CD33) were associated with hematological measurements such as white blood cell (leukocyte) count, monocyte count, neutrophill count, platelet count, and/or mean platelet (thrombocyte) volume (an autoimmune disease biomarker). Many of these genes are expressed specifically in microglia. The associations of ABI3 variant with cardiovascular and immune-related traits are one of the novel findings from this study. Taken together, it is evidenced that at least some AD and FTD variants are associated with multiple clinical phenotypes and not just dementia. These findings were discussed in the context of causal relationship versus pleiotropy via Mendelian randomization analysis.