Prevalence of rearrangements in the 22q11.2 region and population-based risk of neuropsychiatric and developmental disorders in a Danish population: a case-cohort study.
Prevalence of rearrangements in the 22q11.2 region and population-based risk of neuropsychiatric and developmental disorders in a Danish population: a case-cohort study.
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DOI：
10.1016/s2215-0366(18)30168-8
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发表时间：
2018-07
期刊：
影响因子：
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通讯作者：
Werge T
中科院分区：
文献类型：
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作者：
Olsen L;Sparsø T;Weinsheimer SM;Dos Santos MBQ;Mazin W;Rosengren A;Sanchez XC;Hoeffding LK;Schmock H;Baekvad-Hansen M;Bybjerg-Grauholm J;Daly MJ;Neale BM;Pedersen MG;Agerbo E;Mors O;Børglum A;Nordentoft M;Hougaard DM;Mortensen PB;Geschwind DH;Pedersen C;Thompson WK;Werge T
虽然染色体22q11.2上的CNV的致病性已经被认识了几十年，但缺乏对其人群患病率、死亡率、疾病风险和诊断轨迹的无偏估计。因此，我们的目标是利用无偏的、具有代表性的丹麦iPSYCH人群病例队列，提供22q11.2 CNV的真实人群患病率、疾病风险轨迹和死亡率。我们使用流行病学方法结合全国医院登记来分析iPSYCH病例对照队列，即1981年至2005年出生的病例（n= 57，377）患有注意力缺陷/多动障碍，重度抑郁症，精神分裂症，自闭症或双相情感障碍以及30，000名随机抽取的个体-以提供无偏倚，主要神经精神疾病的人口调整估计值和30年的疾病轨迹。在丹麦人群中，缺失和重复的人群患病率分别为1：3672和1：1606，死亡率为零，神经精神疾病的风险比范围为1至82倍。到32岁时，10%的人患上注意力缺陷/多动障碍、自闭症或智力残疾;缺失携带者患智力残疾和癫痫的概率高于重复携带者。22q11.2重复和缺失的显着不同的患病率表明这些重排不同的选择性压力。虽然先天性异常，发育迟缓和智力残疾的风险是在删除载体升高，神经精神疾病的总体患病率是较高的复制载体，这意味着识别和临床监测应超越先天性特征，并进入儿童和青少年精神病学。
While the pathogenic nature of CNVs on chromosome 22q11.2 have been recognized for decades, unbiased estimates of their population prevalence, mortality, disease risks, and diagnostic trajectories are lacking. Hence, we aim to provide the true population prevalence, trajectory of disease risk, and mortality of 22q11.2 CNVs utilizing the unbiased, representative Danish iPSYCH population case-cohort. We use epidemiological methods in conjunction with nationwide hospital registers to analyze the iPSYCH case-control cohort i.e. cases born from 1981 to 2005 (n=57,377) with Attention-Deficit/Hyperactivity Disorder, Major Depressive Disorder, Schizophrenia, Autism or Bipolar Disorder as well as 30,000 randomly drawn individuals – to provide unbiased, population-adjusted estimates and 30-year long disease trajectories for major neuropsychiatric disorders. Population prevalence in the Danish population was 1:3672 and 1:1606 for deletions and duplications, respectively, the mortality rate was zero and hazard ratios for neuropsychiatric disorders ranged from 1 to 82 comparably for both rearrangements. By age 32, 10% developed Attention-Deficit/Hyperactivity Disorder, Autism or Intellectual Disability; and deletion carriers had higher probability than duplication carriers of co-occurring Intellectual Disability and of epilepsy. The significantly different prevalence of 22q11.2 duplications and deletions indicates distinct selective pressures on these rearrangements. While risk for congenital abnormalities, developmental delay, and Intellectual Disability is elevated in deletion carriers, the overall prevalence of neuropsychiatric disorders is higher in duplication carriers, which implies that identification and clinical monitoring should extend beyond congenital traits and into child and adolescent psychiatry.