Genomics of body fat percentage may contribute to sex bias in anorexia nervosa
Genomics of body fat percentage may contribute to sex bias in anorexia nervosa
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DOI：
10.1002/ajmg.b.32709
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发表时间：
2019-09-01
影响因子：
2.8
通讯作者：
Breen, Gerome
中科院分区：
文献类型：
--
作者：
Hubel, Christopher;Gaspar, Helena A.;Breen, Gerome
神经性厌食症（AN）在女性中的发生率是男性的9倍。虽然环境因素可能发挥了作用，但这种性别比例失衡的原因仍然没有得到解决。AN显示出与人体测量和代谢性状的高度遗传相关性。鉴于身体成分的性别差异，我们研究了女性AN倾向的可能代谢基础。我们在英国生物库的健康和无药物子样本（n = 155，961）中进行了性别特异性GWAS，确定了77个与体脂百分比（BF%）相关的全基因组显著位点和174个与无脂肪质量（FFM）相关的基因组显著位点。分区遗传力分析表明，富集的中枢神经组织相关基因的BF%，这是更突出的女性比男性。估计BF%和FFM与精神病基因组学联盟的AN的最大GWAS的遗传相关性以探索共享基因组学。BF%（男性）和BF%（女性）与AN的遗传相关性彼此之间存在显著差异（p < .0001，δ = -0.17），表明女性在AN中的优势可能部分由性别特异性人体测量和代谢遗传因素增加对AN的易感性来解释。
Anorexia nervosa (AN) occurs nine times more often in females than in males. Although environmental factors likely play a role, the reasons for this imbalanced sex ratio remain unresolved. AN displays high genetic correlations with anthropometric and metabolic traits. Given sex differences in body composition, we investigated the possible metabolic underpinnings of female propensity for AN. We conducted sex-specific GWAS in a healthy and medication-free subsample of the UK Biobank (n = 155,961), identifying 77 genome-wide significant loci associated with body fat percentage (BF%) and 174 with fat-free mass (FFM). Partitioned heritability analysis showed an enrichment for central nervous tissue-associated genes for BF%, which was more prominent in females than males. Genetic correlations of BF% and FFM with the largest GWAS of AN by the Psychiatric Genomics Consortium were estimated to explore shared genomics. The genetic correlations of BF%(male) and BF%(female) with AN differed significantly from each other (p < .0001, delta = -0.17), suggesting that the female preponderance in AN may, in part, be explained by sex-specific anthropometric and metabolic genetic factors increasing liability to AN.