Levinson D F, Mahtani M M, Nancarrow D J, Brown D M, Kruglyak L, Kirby A, Hayward N K, Crowe R R, Andreasen N C, Black D W, Silverman J M, Endicott J, Sharpe L, Mohs R C, Siever L J, Walters M K, Lennon D P, Jones H L, Nertney D A, Daly M J, Gladis M, Mowry B J
Department of Psychiatry, Allegheny University of the Health Sciences, Philadelphia, USA.
Am J Psychiatry. 1998 Jun;155(6):741-50. doi: 10.1176/ajp.155.6.741.
The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes.
A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals--126 of them with schizophrenia-related psychoses--from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease.
Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002).
The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.
本研究的目的是确定可能包含精神分裂症易感基因的染色体区域。
对来自43个家系的269名个体（其中126名患有精神分裂症相关精神病）进行了平均间距为11厘摩的310个微卫星DNA标记的全基因组图谱基因分型。采用非参数连锁分析来评估每个标记位点上等位基因共享模式与疾病存在情况的相关性。
对于任何标记，非参数连锁分数均未达到全基因组水平的统计学显著性。有五个染色体区域，在八个标记位置上，经验得出的p值达到了名义显著性水平。在2号染色体q臂（该区域峰值位于D2S410）和10号染色体q臂（D10S1239）上p值小于0.01，在4号染色体q臂（D4S2623）、9号染色体q臂（D9S257）和11号染色体q臂（D11S2002）上p值小于0.05。
结果不支持单一基因导致精神分裂症风险大幅增加的假说。该样本（与大多数正在研究的精神疾病样本一样）检测小效应基因或在一小部分家庭中起风险决定作用的基因的能力有限。所有最显著的结果可能是由于偶然因素，或者有些可能反映了弱连锁（小效应基因）。多中心研究可能有助于确定最有可能包含精神分裂症易感基因的染色体区域。
