Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study.
Associations of psychiatric disorders with sex chromosome aneuploidies in the Danish iPSYCH2015 dataset: a case-cohort study.
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丹麦 iPSYCH2015 数据集中精神疾病与性染色体非整倍体的关联：病例队列研究。
DOI：
10.1016/s2215-0366(23)00004-4
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Thompson,Wesley
中科院分区：
文献类型：
--
作者：
Sánchez,XabierCalle;Montalbano,Simone;Vaez,Morteza;Krebs,MortenDybdahl;Byberg-Grauholm,Jonas;Mortensen,PrebenB;Børglum,AndersD;Hougaard,DavidM;Nordentoft,Merete;Geschwind,DanielH;Buil,Alfonso;Schork,AndrewJ;Thompson,Wesley
研究背景在性染色体非整倍体的临床研究中已经报道了精神疾病的患病率增加，但是需要对性染色体非整倍体的患病率和临床检出率以及精神疾病的相关风险进行基于人群的准确估计。在这项研究中，我们提供了这样的估计，有效的儿童和年轻人的当代Danish population.MethodsWe使用的iPSYCH 2015年的情况下，队列数据集，这是基于一个源人口出生在丹麦之间的1981年5月1日，2008年12月31日。病例样本包括在随访结束时（2015年12月31日）诊断为任何指数精神障碍（精神分裂症谱系障碍，双相情感障碍，重度抑郁症，自闭症谱系障碍或ADHD）的源人群中的所有个体，在基于医院的丹麦精神病学中央研究登记处登记。队列由从源人群中随机选择的个体组成，并与病例样本重叠。对病例中个体的生物库血液样本和队列样本进行基因分型和质量控制过滤，之后我们分析微阵列数据以检测性染色体非整倍性核型（45，X，47，XXX，47，XXY和47，XYY）。我们从队列样本中估计了这些核型的人群有效患病率。采用加权考克斯比例风险模型估计与每种性染色体非整倍体核型相关的每种指数精神疾病的风险，以相应病例组和队列中指数疾病的首次住院日期作为结局。临床检测率是通过将丹麦国家患者登记处的遗传性疾病临床诊断记录与我们研究确定的性染色体非整倍体核型进行比较来确定的。结果评估样本包括119481名个体（病例样本中有78726人，队列中有43326人）进行了基因分型和质量控制过滤的血液样本，其中包括64533人（54%）性腺男性和54948人（46%）性腺女性。 随访期间的年龄范围为0 - 34.7岁（平均10.9岁[SD 3.5岁]）。没有关于族裔的资料。我们确定了387例（0.3%）性染色体非整倍性携带者。性染色体非整倍体的总患病率为1.5/1000个体。每一个性染色体非整倍体核型与至少一种精神疾病指标的风险增加相关，风险比（HR）为2.20（95% CI 1.42 - 3.39），47，XXY; 2.73（1.25 - 6.00），47，XXX; 3.56（1.01 - 12.53），45，X; 4.30（2.48 - 7.55），47，XYY。所有的核型都与ADHD的风险增加有关（HR范围为1·99 [1·24-3·19]至6·15 [1·63-23·19]），自闭症谱系障碍（2·72 [1·72-4·32]至8·45 [2·49-28·61]）和精神分裂症谱系障碍（1·80 [1·15-2·80]至4·60 [1·57-13·51]）。47，XXY（1.88 [1.07 - 3.33]）和47，XYY（2.65 [1.12 - 5.90]）的个体患重度抑郁症的风险增加，47，XXX的个体患双相情感障碍的风险增加（4.32 [1.12 - 16.62]）。临床诊断的性染色体非整倍体携带者比例为45，X为93%，但47，XXY（22%），47，XXX（15%）和47，XYY（15%）较低。在携带者中，诊断为至少一种指数精神障碍的风险在临床诊断为性染色体非整倍体和未诊断为性染色体非整倍体的患者之间没有显著差异（p= 0.65）。
BackgroundIncreased prevalence of mental illness has been reported in clinical studies of sex chromosome aneuploidies, but accurate population-based estimates of the prevalence and clinical detection rate of sex chromosome aneuploidies and the associated risks of psychiatric disorders are needed. In this study, we provide such estimates, valid for children and young adults of the contemporary Danish population.MethodsWe used the iPSYCH2015 case-cohort dataset, which is based on a source population of single-born individuals born in Denmark between May 1, 1981, and Dec 31, 2008. The case sample comprises all individuals from the source population with a diagnosis of any index psychiatric disorder (schizophrenia spectrum disorder, bipolar disorder, major depressive disorder, autism spectrum disorder, or ADHD) by the end of follow-up (Dec 31, 2015), registered in the hospital-based Danish Psychiatric Central Research Register. The cohort consists of individuals randomly selected from the source population, and overlaps with the case sample. Biobanked blood samples for individuals in the case and cohort samples underwent genotyping and quality-control filtering, after which we analysed microarray data to detect sex chromosome aneuploidy karyotypes (45,X, 47,XXX, 47,XXY, and 47,XYY). We estimated the population-valid prevalence of these karyotypes from the cohort sample. Weighted Cox proportional hazards models were used to estimate the risks of each index psychiatric disorder associated with each sex chromosome aneuploidy karyotype, by use of date of first hospitalisation with the index disorder in the respective case group and the cohort as outcome. The clinical detection rate was determined by comparing records of clinical diagnoses of genetic conditions from the Danish National Patient Register with sex chromosome aneuploidy karyotype determined by our study.FindingsThe assessed sample comprised 119 481 individuals (78 726 in the case sample and 43 326 in the cohort) who had genotyped and quality-control-filtered blood samples, including 64 533 (54%) people of gonadal male sex and 54 948 (46%) of gonadal female sex. Age during follow-up ranged from 0 to 34·7 years (mean 10·9 years [SD 3·5 years]). Information on ethnicity was not available. We identified 387 (0·3%) individuals as carriers of sex chromosome aneuploidies. The overall prevalence of sex chromosome aneuploidies was 1·5 per 1000 individuals. Each sex chromosome aneuploidy karyotype was associated with an increased risk of at least one index psychiatric disorder, with hazard ratios (HRs) of 2·20 (95% CI 1·42–3·39) for 47,XXY; 2·73 (1·25–6·00) for 47,XXX; 3·56 (1·01–12·53) for 45,X; and 4·30 (2·48–7·55) for 47,XYY. All karyotypes were associated with an increased risk of ADHD (HRs ranging from 1·99 [1·24–3·19] to 6·15 [1·63–23·19]), autism spectrum disorder (2·72 [1·72–4·32] to 8·45 [2·49–28·61]), and schizophrenia spectrum disorder (1·80 [1·15–2·80] to 4·60 [1·57–13·51]). Increased risk of major depressive disorder was found for individuals with 47,XXY (1·88 [1·07–3·33]) and 47,XYY (2·65 [1·12–5·90]), and of bipolar disorder for those with 47,XXX (4·32 [1·12–16·62]). The proportion of sex chromosome aneuploidy carriers who had been clinically diagnosed was 93% for 45,X, but lower for 47,XXY (22%), 47,XXX (15%), and 47,XYY (15%). Among carriers, the risk of diagnosis of at least one index psychiatric disorder did not significantly differ between those who had and had not been clinically diagnosed with sex chromosome aneuploidies (p=0·65).InterpretationIncreased risks of psychiatric disorders associated with sex …
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作者：
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作者：
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DOI：
10.1016/s2215-0366(18)30168-8
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
Werge T
DOI：
10.1002/ajmg.a.33334
发表时间：
2010-05
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Ottesen AM;Aksglaede L;Garn I;Tartaglia N;Tassone F;Gravholt CH;Bojesen A;Sørensen K;Jørgensen N;Rajpert-De Meyts E;Gerdes T;Lind AM;Kjaergaard S;Juul A
通讯作者：
Juul A