DNA RISK FACTORS IN YOUTH SUICIDE

该建议旨在确定导致青少年自杀风险的遗传风险因素（基因多态性）。目前正在研究两种方法，每一种方法都检测犹他州自杀受害者的候选基因。方法包括单倍型相对风险分析和直接突变分析。先前的研究表明，导致自杀的因素既有环境因素，也有遗传因素。血清素能系统与冲动和自杀行为有关，而色氨酸羟化酶（TPH）是合成血清素的限速酶。首席研究员已经检测到TPH基因内含子7的多态性，并在犹他州青少年自杀研究的66名自杀受害者样本中进行了研究。对该基因及其周围几个位点多态性的研究表明，该基因似乎与该人群的自杀行为无关。目前正在寻找其他基因座。这些研究的DNA是从验尸官办公室（位于大学医学中心）提供的死后血液或其他组织中获得的。在另一项经IRB批准的名为“犹他州青少年和年轻人自杀调查的社区方法”（IRB #5698-95）的研究中，从自杀受害者的先证者的血统成员中收集血液。

This proposal was designed to identify hereditary risk factors (genetic polymorphisms) that contribute to risk of youth suicide. Two methods are under study, each examining candidate genes in Utah's suicide victims. The methods include haplotype relative risk and direct mutation analysis. Previous research has indicated that factors contributing to suicide are both environmental and inherited. The serotonergic system has been implicated in impulsivity and suicidality, and tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. The Principal Investigator has detected polymorphisms in intron 7 of the TPH gene, and this was studied in a sample of 66 suicide victims from the Utah Youth Suicide Study. Studies of polymorphisms at several loci in and surrounding this gene did not appear to be associated with suicide in this population. Additional loci are now being sought. DNA for these studies is obtained from post-mortem blood or other tissues made available through the Medical Examiner's office (located at the University Medical Center). Blood from pedigree members of probands who were suicide victims is collected under another IRB-approved study, entitled "A Community Approach for Investigating Suicide Among Teenagers and Young Adults in Utah" (IRB #5698-95).