Mérette C, Roy-Gagnon M H, Ghazzali N, Savard F, Boutin P, Roy M A, Maziade M
Centre de Recherche Université Laval Robert-Giffard, Québec, Canada.
Am J Med Genet. 2000 Feb 7;96(1):61-8.
Anticipation was investigated in schizophrenia (SZ) and bipolar disorder (BP) while addressing several biases in 18 large families (154 subjects) from Eastern Québec densely affected by SZ, BP, or both over three generations. In particular, we controlled for an information bias using a measure of quality and quantity of clinical information (QOI) concerning the subjects' illness. Otherwise, spurious anticipation could have arisen because we found that QOI varied with the generations as well as with the severity of illness. Although anticipation was investigated separately for SZ and BP, both disorders were also included in one analysis that tested anticipation under the unitary hypothesis that the SZ and the BP spectrums represent a continuum of severity of the same disease. Age of onset (AOO) and five indices of severity were tested for anticipation. Two statistics were used: the difference in the mean AOO or severity between two successive generations, and the mean difference in parent-offspring pairs (POP). The study led to four main findings: 1) the choice of the statistics greatly influenced the results, POP yielding systematically greater biased estimates; 2) for SZ and BP, the evidence for anticipation with the five severity indices vanished after controlling for QOI; 3) as regards AOO a decrease of 8.6 years, p = 0.0001, and 5.3 years, p = 0.009 in AOO was found for SZ between Generations 1-2, and 2-3, respectively, despite controlling for QOI and addressing all biases; and 4) conversely for BP, anticipation with AOO may be due to censoring. Findings suggest that future anticipation studies should also control for QOI. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:61-68, 2000.
在魁北克东部的18个大家庭（154名受试者）中，对精神分裂症（SZ）和双相情感障碍（BP）的遗传早现现象进行了研究，这些家庭在三代人中受到SZ、BP或两者的严重影响。特别是，我们使用了一种关于受试者疾病的临床信息质量和数量（QOI）的测量方法来控制信息偏差。否则，可能会出现虚假的遗传早现现象，因为我们发现QOI会随着代际以及疾病的严重程度而变化。尽管对SZ和BP的遗传早现现象分别进行了研究，但这两种疾病也被纳入了一项分析中，该分析在单一假设下测试遗传早现现象，即SZ和BP谱系代表同一种疾病严重程度的连续体。对发病年龄（AOO）和五个严重程度指标进行了遗传早现测试。使用了两种统计方法：连续两代之间平均AOO或严重程度的差异，以及亲子对（POP）中的平均差异。该研究得出了四个主要发现：1）统计方法的选择对结果有很大影响，POP产生的偏差估计值系统地更大；2）对于SZ和BP，在控制QOI后，五个严重程度指标的遗传早现证据消失；3）关于AOO，尽管控制了QOI并解决了所有偏差，但在第1代至第2代和第2代至第3代之间，SZ的AOO分别下降了8.6岁（p = 0.0001）和5.3岁（p = 0.009）；4）相反，对于BP，AOO的遗传早现可能是由于审查造成的。研究结果表明，未来的遗传早现研究也应该控制QOI。《美国医学遗传学杂志》（神经精神遗传学）96:61 - 68，2000年。
