Y染色体单倍群与注意缺陷多动障碍的关联研究

注意缺陷多动障碍（ADHD）是多基因共同作用的复杂性遗传疾病。该病在临床流行病学、神经心理学和神经影像学等维度均存在明显的性别差异。Y染色体作为两性遗传物质差异最显著的成分，与大脑发育的性别差异有关。动物实验、神经生物学及分子遗传学等多方面证据提示Y染色体极有可能参与ADHD的病理发病机制，特别是男性ADHD患者多见的冲动、攻击性等。本研究拟在2000例ADHD男性患儿及1000名男性正常对照中，对Y染色体15个多态性位点进行检测，探讨Y染色体单倍群与ADHD及其亚型的关联；同时，在其中1000例ADHD及500名年龄匹配的对照中，将冲动/抑制缺陷、攻击性作为候选内表型，探讨其与Y染色体单倍群的关联。通过上述研究，预期将Y染色体纳入ADHD遗传易感性图谱，深入了解ADHD存在明显性别差异的分子基础，进而探讨其潜在的病理机制；同时，对其他存在性别差异的神经精神疾病的研究也具有一定的指导意义。

Attention-deficit/hyperactivity disorder (ADHD) is a complex heritable disease affected by multiple genes. Studies of clinical epidemiology, neuropsychology and neuroimaging have indicated obvious gender difference of ADHD. Y chromosome, which is the most distinct component of genetic materials between males and females, has been suggested to be associated with the gender difference of brain development. Abundant evidence from animal model, neurochemistry and molecular genetics has indicated the possible influence of Y chromosome genetic variants on the physiopathologic mechanism of ADHD, especially for impulsivity and aggression which is more common for males. In the present study, 15 binary markers of Y chromosome will be genotyped for 2,000 male ADHD cases and 1,000 male controls to explore the possible association between Y chromosome haplogroups and ADHD. In addition, we will also analyze the association of Y chromosome haplogroups with impulsivity and aggression of ADHD in 1,000 male cases and 500 age-matched male controls. We anticipate enrolling Y chromosome genetic variants into the genetic susceptibility map of ADHD to help us to understand the genetic mechanism of its gender difference, and to explore the underlying etiology and pathogenesis of ADHD. What's more, it may be also significant and helpful for the research of other neuropsychiatric diseases with gender difference.