Expression data for 2 obese subjects from the SibPair cohort with a deletion on 16p11.2. Homo sapiens

We report a highly-penetrant form of obesity, initially observed in 31 heterozygous carriers of a 593kb or larger deletion at 16p11.2 from amongst subjects ascertained for cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16053 individuals from 8 European cohorts; such deletions was absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (p = 6.4x10-8, OR = 43). These findings highlight a promising strategy for identifying missing heritability in obesity and other complex traits, in which insights from rare extreme cases can be used to elucidate the basis for more common phenotypes. Overall design: The expression data was analysed for 2 obese subjects carrying a deletion on 16p11.2. There are no replicates or controls.

本研究报道了一种外显率极高的肥胖表型，最初在因认知缺陷纳入的受试者中，于31名携带16p11.2区域593kb及以上大片段缺失的杂合携带者中被发现。研究团队从8个欧洲队列共16053名个体的全基因组关联研究（Genome-Wide Association Study, GWAS）数据中，额外鉴定出19例同类染色体缺失。此类缺失在健康非肥胖对照人群中完全不存在，且在本研究的病态肥胖病例中占比达0.7%（p=6.4×10^-8，比值比OR=43）。上述结果为解析肥胖及其他复杂性状的缺失遗传力提供了极具前景的策略：即通过罕见极端病例的研究线索，阐明更为普遍的临床表型的遗传基础。实验整体设计：本研究对2名携带16p11.2区域缺失的肥胖受试者的基因表达数据进行了分析，未设置生物学重复与对照样本。