美国加州大学洛杉矶分校Nelson B. Freimer密歇根大学Michael Boehnke研究小组宣布，他们通过外显子组测序，识别了芬兰人群中的有害等位基因。该项研究成果发表在2019年8月15日出版的《自然》上。

芬兰北部和东部的人口在突破隔离瓶颈后已经大大增加，这些种群中的个体上的许多有害等位基因处于较高的频率。研究人员利用来自这些区域的近20000个个体的外显子序列，研究了罕见的编码变异在临床相关的定量心脏代谢特征中的作用。外显子关联分析64个数量性状识别出26个新的相关有害等位基因，在这26个等位基因中，19个是芬兰个体特有的或者是芬兰种群里远高于其他欧洲种群的。

据了解，外显子测序研究通常缺乏识别有害等位基因的能力，这些等位基因对复杂性状的影响很大，又大多是罕见的。

附：英文原文

Title: Exome sequencing of Finnish isolates enhances rare-variant association power

Author: Adam E. Locke, Karyn Meltz Steinberg, Charleston W. K. Chiang, Susan K. Service, Aki S. Havulinna, Laurel Stell, Matti Pirinen, Haley J. Abel, Colby C. Chiang, Robert S. Fulton, Anne U. Jackson, Chul Joo Kang, Krishna L. Kanchi, Daniel C. Koboldt, David E. Larson, Joanne Nelson, Thomas J. Nicholas, Arto Pietilä, Vasily Ramensky, Debashree Ray, Laura J. Scott, Heather M. Stringham, Jagadish Vangipurapu, Ryan Welch, Pranav Yajnik, Xianyong Yin, Johan G. Eriksson, Mika Ala-Korpela, Marjo-Riitta Järvelin, Minna Männikkö, Hannele Laivuori, FinnGen Project, Susan K. Dutcher, Nathan O. Stitziel, Richard K. Wilson, Ira M. Hall, Chiara Sabatti, Aarno Palotie, Veikko Salomaa, Markku Laakso, Samuli Ripatti, Michael Boehnke, Nelson B. Freimer 

Issue&Volume: Volume 572 Issue 7769

Abstract: Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power.

DOI: 10.1038/s41586-019-1457-z

Source: https://www.nature.com/articles/s41586-019-1457-z