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Genomics of body fat percentage may contribute to sex bias in anorexia nervosa.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ( IF 2.8 ) Pub Date : 2018-12-28 , DOI: 10.1002/ajmg.b.32709
Christopher Hübel 1, 2, 3 , Héléna A Gaspar 1, 2 , Jonathan R I Coleman 1, 2 , Hilary Finucane 4 , Kirstin L Purves 1 , Ken B Hanscombe 5 , Inga Prokopenko 6 , , Mariaelisa Graff 7 , Julius S Ngwa 8, 9 , Tsegaselassie Workalemahu 10 , , , , , Paul F O'Reilly 1 , Cynthia M Bulik 3, 11, 12 , Gerome Breen 1, 2
Affiliation  

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, δ = -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.

中文翻译:

身体脂肪百分比的基因组学可能导致神经性厌食症的性别偏见。

女性神经性厌食症 (AN) 的发生率是男性的九倍。尽管环境因素可能发挥了作用,但造成这种性别比例失衡的原因仍未解决。AN 与人体测量和代谢特征具有高度的遗传相关性。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。我们在英国生物银行的健康且无药物的子样本 (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%) 相关的全基因组显着位点和 174 个与去脂体重 (FFM) 相关的位点。分区遗传力分析显示 BF% 的中枢神经组织相关基因富集,这在女性中比男性更为突出。精神病学基因组学联盟估计了 BF% 和 FFM 与 AN 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 的遗传相关性彼此显着不同 (p < .0001, δ = -0.17),表明 AN 中女性的优势部分可以通过性别特异性的人体测量学和代谢遗传因素增加 AN 的易感性。
更新日期:2019-11-01
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