Breton Édith, Kaufmann Tobias
Centre for Precision Psychiatry, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Fundamental Sciences, Université du Québec à Chicoutimi, Saguenay, QC, Canada.
Transl Psychiatry. 2025 Feb 19;15(1):59. doi: 10.1038/s41398-025-03270-1.
Anorexia nervosa (AN) typically emerges around adolescence and predominantly affects females. Recent progress has been made in identifying biological correlates of AN, but more research is needed to pinpoint the specific mechanisms that lead to its development and maintenance. There is a known phenotypic link between AN, growth and sexual maturation, yet the genetic overlap between these phenotypes remains enigmatic. One may hypothesize that shared factors between AN, energy metabolism and reproductive functions may have been under recent evolutionary selection. Here, we characterize the genetic overlap between AN, BMI and age at menarche, and aimed to reveal recent evolutionary factors that may help explain the origin of AN. We obtained publicly available GWAS summary statistics of AN, BMI and age at menarche and studied the polygenic overlap between them. Next, we used Neandertal Selective Sweep scores to explore recent evolutionary selection. We found 22 loci overlapping between AN and BMI, and 9 loci between AN and age at menarche, with 7 of these not previously associated with AN. We found that loci associated with AN may have been under particular evolutionary dynamic. Chronobiology appeared relevant to the studied genetic overlaps and prone to recent evolutionary selection, offering a promising avenue for future research. Taken together, our findings contribute to the understanding of the genetic underpinning of AN. Ultimately, better knowledge of the biological origins of AN may help to target specific biological processes and facilitate early intervention in individuals who are most at risk.
神经性厌食症（AN）通常在青春期前后出现，主要影响女性。在确定AN的生物学关联方面最近取得了进展，但仍需要更多研究来查明导致其发生和维持的具体机制。AN、生长和性成熟之间存在已知的表型联系，然而这些表型之间的遗传重叠仍然不明。有人可能会假设，AN、能量代谢和生殖功能之间的共同因素可能在近期的进化选择之下。在此，我们描述了AN、体重指数（BMI）和初潮年龄之间的遗传重叠，并旨在揭示可能有助于解释AN起源的近期进化因素。我们获取了公开可用的关于AN、BMI和初潮年龄的全基因组关联研究（GWAS）汇总统计数据，并研究了它们之间的多基因重叠。接下来，我们使用尼安德特人选择清除分数来探索近期的进化选择。我们发现AN和BMI之间有22个重叠位点，AN和初潮年龄之间有9个重叠位点，其中7个此前未与AN相关联。我们发现与AN相关的位点可能处于特定的进化动态之下。生物钟学似乎与所研究的遗传重叠相关，并且易于受到近期的进化选择，为未来研究提供了一个有前景的途径。综上所述，我们的发现有助于理解AN的遗传基础。最终，更好地了解AN的生物学起源可能有助于针对特定的生物学过程，并促进对最具风险个体的早期干预。
