Genes have great significance for the prevention and treatment of some diseases. A vital consideration is the need to find a way to locate pathogenic genes by analyzing the genetic data obtained from different medical institutions while protecting the privacy of patients’ genetic data. In this paper, we present a secure scheme for locating disease-causing genes based on Multi-Key Homomorphic Encryption (MKHE), which reduces the risk of leaking genetic data. First, we combine MKHE with a frequency-based pathogenic gene location function. The medical institutions use MKHE to encrypt their genetic data. The cloud then homomorphically evaluates specific gene-locating circuits on the encrypted genetic data. Second, whereas most location circuits are designed only for locating monogenic diseases, we propose two location circuits (TH-intersection and Top-q) that can locate the disease-causing genes of polygenic diseases. Third, we construct a directed decryption protocol in which the users involved in the homomorphic evaluation can appoint a target user who can obtain the final decryption result. Our experimental results show that compared to the JWB+17 scheme published in the journal Science, our scheme can be used to diagnose polygenic diseases, and the participants only need to upload their encrypted genetic data once, which reduces the communication traffic by a few hundred-fold.