Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.
Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.
复制标题
在秘鲁混合人群中，分析美洲印第安人遗传祖先和ApoE ε4等位基因对阿尔茨海默病的作用。
DOI：
10.1016/j.neurobiolaging.2020.10.003
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发表时间：
2021-05
影响因子：
4.2
通讯作者：
Pericak-Vance MA
中科院分区：
文献类型：
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作者：
Marca-Ysabel MV;Rajabli F;Cornejo-Olivas M;Whitehead PG;Hofmann NK;Illanes Manrique MZ;Veliz Otani DM;Milla Neyra AK;Castro Suarez S;Meza Vega M;Adams LD;Mena PR;Rosario I;Cuccaro ML;Vance JM;Beecham GW;Custodio N;Montesinos R;Mazzetti Soler PE;Pericak-Vance MA
Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic White (NHW) populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first three principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and ε4 allele is significantly associated with increased risk of AD in the Peruvian population (OR = 5.02, CI: 2.3–12.5, p-value = 2e–4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in NHW populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.
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影响因子：
5.8
作者：
Gogarten, Stephanie M.;Sofer, Tamar;Conomos, Matthew P.
通讯作者：
Conomos, Matthew P.
影响因子：
4.5
作者：
Homburger JR;Moreno-Estrada A;Gignoux CR;Nelson D;Sanchez E;Ortiz-Tello P;Pons-Estel BA;Acevedo-Vasquez E;Miranda P;Langefeld CD;Gravel S;Alarcón-Riquelme ME;Bustamante CD
通讯作者：
Bustamante CD
DOI：
10.1212/nxg.0000000000000079
发表时间：
2016-06
期刊：
Neurology. Genetics
影响因子：
--
作者：
Cukier HN;Kunkle BW;Vardarajan BN;Rolati S;Hamilton-Nelson KL;Kohli MA;Whitehead PL;Dombroski BA;Van Booven D;Lang R;Dykxhoorn DM;Farrer LA;Cuccaro ML;Vance JM;Gilbert JR;Beecham GW;Martin ER;Carney RM;Mayeux R;Schellenberg GD;Byrd GS;Haines JL;Pericak-Vance MA;Alzheimer's Disease Genetics Consortium
通讯作者：
Alzheimer's Disease Genetics Consortium
影响因子：
5.4
作者：
Holtzman, David M.;Herz, Joachim;Bu, Guojun
通讯作者：
Bu, Guojun
影响因子：
9.8
作者：
Maples, Brian K.;Gravel, Simon;Bustamante, Carlos D.
通讯作者：
Bustamante, Carlos D.