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Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa
American Journal of Psychiatry ( IF 15.1 ) Pub Date : 2017-05-12 , DOI: 10.1176/appi.ajp.2017.16121402
Laramie Duncan 1 , Zeynep Yilmaz 1 , Helena Gaspar 1 , Raymond Walters 1 , Jackie Goldstein 1 , Verneri Anttila 1 , Brendan Bulik-Sullivan 1 , Stephan Ripke 1 , 1 , Laura Thornton 1 , Anke Hinney 1 , Mark Daly 1 , Patrick F Sullivan 1 , Eleftheria Zeggini 1 , Gerome Breen 1 , Cynthia M Bulik 1
Affiliation  

Objective:

The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.

Method:

Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.

Results:

Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.

Conclusions:

Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.



中文翻译:


神经性厌食症的全基因组关联研究揭示了显着的位点和代谢遗传相关性


 客观的:


作者对神经性厌食症进行了全基因组关联研究,并计算了与一系列精神、教育和代谢表型的遗传相关性。

 方法:


作者使用千人基因组计划(第 3 阶段)对 12 个病例对照队列(包括 3,495 名神经性厌食症病例和 10,982 名对照)进行统一的质量控制和插补程序,随后进行了标准关联分析,然后进行了跨队列的荟萃分析。使用连锁不平衡评分回归来计算全基因组常见变异遗传力(基于单核苷酸多态性 [SNP] 的遗传力 [h 2 SNP ])、分区遗传力以及神经性厌食症与 159 种其他表型之间的遗传相关性 (r g )。

 结果:


获得了 10,641,224 个 SNP 和插入缺失变异的结果,次要等位基因频率为 >1%,插补质量得分为 >0.6。神经性厌食症的 h 2 SNP为 0.20 (SE=0.02),表明双胞胎遗传力的很大一部分来自共同的遗传变异。作者在 12 号染色体 (rs4622308) 上发现了一个全基因组重要位点,该位点位于先前报道的 1 型糖尿病和自身免疫性疾病位点的区域。神经性厌食症与精神分裂症、神经质、受教育程度和高密度脂蛋白胆固醇之间观察到显着的正向遗传相关性,而神经性厌食症与体重指数、胰岛素、血糖和血脂表型之间观察到显着的负向遗传相关性。

 结论:


神经性厌食症是一种复杂的遗传表型,这项研究发现了第一个全基因组的重要位点。神经性厌食症还与精神表型和代谢特征具有巨大且显着的遗传相关性。研究结果鼓励人们重新概念化这种经常致命的疾病,将其视为同时具有精神和代谢病因的疾病。

更新日期:2017-09-05
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