Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings
Fecundity of Patients With Schizophrenia, Autism, Bipolar Disorder, Depression, Anorexia Nervosa, or Substance Abuse vs Their Unaffected Siblings
复制标题
DOI：
10.1001/jamapsychiatry.2013.268
复制
发表时间：
2013-01-01
期刊：
影响因子：
25.8
通讯作者：
Svensson, Anna C.
中科院分区：
文献类型：
--
作者：
Power, Robert A.;Kyaga, Simon;Svensson, Anna C.
背景：尽管存在强烈的负选择，但尚不清楚导致精神疾病的遗传变异如何在人群中生存。然而，这是了解其病因和设计识别风险变异的研究的关键。目的：检查精神分裂症和其他精神疾病患者与其未受影响的兄弟姐妹的生殖适应性，并评估因果遗传变异的选择水平。设计：我们测量了精神分裂症、自闭症、双相情感障碍、抑郁症、神经性厌食症或药物滥用患者及其未受影响的患者的生育能力。背景：瑞典的人口数据库，包括多代登记册和瑞典医院出院登记册。参与者：瑞典 1950 年至 1970 年出生队列中总共有 230 万人。主要结果指标：生育率 (FR)，反映与总人口相比的平均儿童数量，考虑了年龄、性别、家庭规模和受影响状况。结果：除患有抑郁症的妇女外，受影响的妇女患者的子女数量明显减少（精神疾病患者的 FR 范围为 0.23-0.93；P < 10(-10)）。男性的这种下降幅度始终大于女性，这表明男性的健康状况特别敏感。尽管精神分裂症和双相情感障碍患者的姐妹的生育能力有所增加（FR范围，1.02-1.03；P
Context: It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants.Objectives: To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants.Design: We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population.Setting: Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register.Participants: In total, 2.3million individuals among the 1950 to 1970 birth cohort in Sweden.Main Outcome Measures: Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status.Results: Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10(-10)). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P