High-throughput sequencing and genome-wide association studies have revealed a sex bias in human diseases. The underlying molecular mechanisms remain, however, unknown. Here, we cover recent advances in cancer and autoimmunity focusing on intrinsic genetic and epigenetic differences underlying sex biases in human disease. These studies reveal a central role of genome regulatory mechanisms including genome repair, chromosome folding, and epigenetic regulation in dictating the sex bias. These highlight the importance of considering sex as a variable in both basic science and clinical investigations. Understanding the molecular mechanisms underlying sex bias in human diseases will be instrumental in making a first step forwards into the era of personalized medicine.

高通量测序和全基因组关联研究表明，人类疾病具有性别偏见。潜在的分子机制仍然未知。在这里，我们涵盖癌症和自身免疫的最新进展，重点关注人类疾病中性别偏见的内在遗传和表观遗传学差异。这些研究揭示了基因组调控机制（包括基因组修复，染色体折叠和表观遗传调控）在指示性别偏见中的核心作用。这些都凸显了在基础科学和临床研究中将性别视为变量的重要性。了解人类疾病中性别偏见的分子机制将有助于迈向个性化医学时代的第一步。