The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish.
The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish.
复制标题
DOI：
10.1016/j.xhgg.2022.100114
复制
发表时间：
2022-07-14
期刊：
影响因子：
--
通讯作者：
Haines, Jonathan L.
中科院分区：
文献类型：
--
作者：
Osterman, Michael D.;Song, Yeunjoo E.;Adams, Larry D.;Laux, Renee A.;Caywood, Laura J.;Prough, Michael B.;Clouse, Jason E.;Herington, Sharlene D.;Slifer, Susan H.;Lynn, Audrey;Fuzzell, M. Denise;Fuzzell, Sarada L.;Hochstetler, Sherri D.;Miskimen, Kristy;Main, Leighanne R.;Dorfsman, Daniel A.;Ogrocki, Paula;Lerner, Alan J.;Ramos, Jairo;Vance, Jeffery M.;Cuccaro, Michael L.;Scott, William K.;Pericak-Vance, Margaret A.;Haines, Jonathan L.
阿尔茨海默病（AD）是最常见的痴呆症类型，目前估计影响620万美国人。它是美国第六大死亡原因，自2000年以来，AD导致的死亡比例一直在增加，而许多其他主要死亡原因的比例则有所下降或保持不变。AD的风险是多因素的，包括遗传和环境风险因素。虽然APOE ε4仍然是AD的最大遗传风险因素，但超过26个其他基因座与AD风险相关。在这里，我们招募了来自俄亥俄州和印第安纳州的阿米什成年人，以调查AD风险和保护性遗传效应。作为一个典型的实行内婚制的创始人群体，在一般人群中罕见的变异可能在阿米什人群中频率更高。由于阿米什人的发病率略低，发病年龄较晚，他们是研究保护性遗传变异的优秀和独特的人群。我们通过APOE基因型、全基因组显著变异的非APOE遗传风险评分和考虑所有变异的非APOE多基因风险评分，比较了阿米什人和非阿米什人人群的AD风险。我们的研究结果强调了阿米什人与非阿米什人，一般欧洲血统人群相比，APOE的相对影响较小，AD风险的遗传结构不同。
Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States, and the proportion of deaths due to AD has been increasing since 2000, while the proportion of many other leading causes of deaths have decreased or remained constant. The risk for AD is multifactorial, including genetic and environmental risk factors. Although APOE ε4 remains the largest genetic risk factor for AD, more than 26 other loci have been associated with AD risk. Here, we recruited Amish adults from Ohio and Indiana to investigate AD risk and protective genetic effects. As a founder population that typically practices endogamy, variants that are rare in the general population may be of a higher frequency in the Amish population. Since the Amish have a slightly lower incidence and later age of onset of disease, they represent an excellent and unique population for research on protective genetic variants. We compared AD risk in the Amish and to a non-Amish population through APOE genotype, a non-APOE genetic risk score of genome-wide significant variants, and a non-APOE polygenic risk score considering all of the variants. Our results highlight the lesser relative impact of APOE and differing genetic architecture of AD risk in the Amish compared to a non-Amish, general European ancestry population.
登录
查看更多内容
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
5.3
作者：
Courtenay MD;Gilbert JR;Jiang L;Cummings AC;Gallins PJ;Caywood L;Reinhart-Mercer L;Fuzzell D;Knebusch C;Laux R;McCauley JL;Jackson CE;Pericak-Vance MA;Haines JL;Scott WK
通讯作者：
Scott WK
影响因子：
4.4
作者：
Hoffman, Joshua D.;Bailey, Jessica N. Cooke;Haines, Jonathan L.
通讯作者：
Haines, Jonathan L.
影响因子：
2.5
作者：
Ashley-Koch, AE;Shao, Y;Pericak-Vance, MA
通讯作者：
Pericak-Vance, MA
影响因子：
--
作者：
Galvin, James E.;Roe, Catherine M.;Morris, John C.
通讯作者：
Morris, John C.