Department of Genomics of Common Disease, Imperial College London, London, UK.
CNRS, Pasteur Institute of Lille, University of Lille, Lille, France.
Obesity (Silver Spring). 2018 Mar;26(3):474-484. doi: 10.1002/oby.22064.
Consanguinity has been instrumental in the elucidation of many Mendelian genetic diseases. Here, the unique advantage of consanguineous populations was considered in the quest for genes causing obesity.
PubMed was searched for articles relevant to consanguinity and obesity published between 1995 and 2016. Some earlier articles of interest were also consulted.
Although obesity is the most heritable disorder, even in outbred populations, only 2% to 5% of severe obesity cases have so far been proven to be caused by single gene mutations. In some highly consanguineous populations, a remarkably higher proportion of obesity cases because of known and novel monogenic variants has been identified (up to 30%).
Combining the power conferred by consanguinity with current large-capacity sequencing techniques should bring new genetic factors and molecular mechanisms to the fore, unveiling a large part of the yet-elusive neurohumoral circuitry involved in the regulation of energy homeostasis and appetite. Importantly, the undertaking of such initiatives is destined to unfold novel targets for the development of precision medicine relevant to different forms of obesity.
血缘关系在阐明许多孟德尔遗传疾病方面发挥了重要作用。在这里，考虑到血缘人群的独特优势，我们在寻找导致肥胖的基因方面进行了研究。
检索了 1995 年至 2016 年间发表的与血缘关系和肥胖相关的 PubMed 文章。还查阅了一些早期感兴趣的文章。
尽管肥胖是最具遗传性的疾病，但即使在异交人群中，迄今为止，仅有 2%至 5%的严重肥胖病例被证明是由单基因突变引起的。在一些血缘关系非常密切的人群中，由于已知和新的单基因变异，肥胖病例的比例显著增加（高达 30%）。
将血缘关系赋予的力量与当前大容量测序技术相结合，应该会揭示更多新的遗传因素和分子机制，揭示在调节能量平衡和食欲方面涉及的神经激素回路的大部分仍未被发现的部分。重要的是，开展此类计划注定会为开发与不同形式肥胖相关的精准医学开辟新的目标。
