Deletion of a non-imprinted 500kb genomic region at chromosome 15q11.2, between breakpoints 1 and 2 of the Prader-Willi/Angelman locus (BP1-BP2 deletion), has been associated in previous studies with phenotypes including congenital cardiovascular malformations (CVM). Previous studies investigating association between BP1-BP2 deletion and CVM have tended to recruit cases with rarer and more severe CVM phenotypes; the impact of CVM on relatively unselected population cohorts, anticipated to contain chiefly less severe but commoner CHD phenotypes, is relatively unexplored. More precisely defining the impact of BP1-BP2 deletion on CVM risk could be useful to guide genetic counselling, since the deletion is frequently identified in the neurodevelopmental clinic. Using the UK Biobank (UKB) cohort of ~500,000 individuals, we identified individuals with CVM and investigated the association with deletions at the BP1-BP2 locus. In addition, we assessed the association of BP1-BP2 deletions with neuropsychiatric diagnoses, cognitive function and academic achievement. Cases of CVM had an increased prevalence of the deletion compared with controls (0.64%; OR = 1.73 [95% CI 1.08-2.75]; p = 0.03), as did those with neuropsychiatric diagnoses (0.68%; OR = 1.84 [95% CI 1.23-2.75]; p = 0.004). We conclude that BP1-BP2 deletion moderately increases the risk of the generally milder, but commoner, CVM phenotypes seen in this unselected population, in addition to its previously demonstrated association in case/control studies ascertained for CVM.

中文翻译：

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英国生物库中先天性心血管畸形和神经精神表型与 15q11.2 (BP1-BP2) 缺失的关联。

先前的研究表明，染色体 15q11.2 上 Prader-Willi/Angelman 基因座断点 1 和 2 之间的非印记 500kb 基因组区域的缺失（BP1-BP2 缺失）与先天性心血管畸形 (CVM) 等表型相关。 。之前调查 BP1-BP2 缺失与 CVM 之间关联的研究倾向于招募具有更罕见和更严重的 CVM 表型的病例；CVM 对相对未经选择的人群的影响相对尚未被探索，这些人群预计主要包含不太严重但常见的 CHD 表型。更准确地定义 BP1-BP2 缺失对 CVM 风险的影响可能有助于指导遗传咨询，因为这种缺失在神经发育临床中经常被发现。利用英国生物银行 (UKB) 约 500,000 名个体的队列，我们​​鉴定了患有 CVM 的个体，并研究了与 BP1-BP2 基因座缺失的关联。此外，我们评估了 BP1-BP2 缺失与神经精神诊断、认知功能和学业成绩的关联。与对照相比，CVM 病例的缺失发生率更高（0.64%；OR = 1.73 [95% CI 1.08-2.75]；p = 0.03），神经精神诊断病例也是如此（0.68%；OR = 1.84 [95%] CI 1.23-2.75]；p = 0.004）。我们得出的结论是，BP1-BP2 缺失会适度增加在这个未经选择的人群中观察到的通常较温和但较常见的 CVM 表型的风险，此外，它还与先前在确定的 CVM 病例/对照研究中证明的相关性有关。