Novel Alzheimer's disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers.
Novel Alzheimer's disease risk variants identified based on whole-genome sequencing of APOE ε4 carriers.
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DOI：
10.1038/s41398-021-01412-9
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发表时间：
2021-05-19
影响因子：
6.8
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Park JH;Park I;Youm EM;Lee S;Park JH;Lee J;Lee DY;Byun MS;Lee JH;Yi D;Chung SJ;Park KW;Choi N;Kim SY;Yoon W;An H;Kim KW;Choi SH;Jeong JH;Kim EJ;Kang H;Lee J;Kim Y;Lee EA;Seo SW;Na DL;Kim JW
阿尔茨海默病（AD）是一种具有复杂遗传病因的进行性神经退行性疾病。除了载脂蛋白E ε4 （APOE ε4）等位基因外，通过主要在欧洲血统个体中进行的全基因组关联研究（GWAS），还发现了数十个与AD相关的遗传位点。最近，在其他种族群体中进行的几个GWAS显示了重复研究的重要性，这些研究确定了先前建立的风险位点并寻找新的风险位点。APOE分层GWAS产生了新的AD风险位点，这些位点可能被APOE等位基因掩盖或依赖于APOE等位基因。我们对331例AD患者和169例APOE ε4携带者的韩国老年对照进行了全基因组测序（WGS）。基于WGS数据，我们设计了一个定制的AD芯片（cAD芯片），用于对543名AD患者和894名老年对照者进行进一步分析，而不考虑他们的APOE ε4等位基因是否存在。WGS和cAD芯片数据联合分析显示，韩国人群APOE ε4携带者中，SORCS1和CHD2基因中的snp rs1890078 （P = 6.64E−07）和rs12594991 （P = 2.03E−07）分别为新的遗传变异。此外，还发现了9种可能的新变异，这些变异在欧洲血统的个体中很少见，但在东亚很常见。该研究表明，apoe分层分析对于了解不同人群AD的遗传背景具有重要意义。
Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E−07) and rs12594991 (P = 2.03E−07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.
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CHD2对于神经回路的发展和长期记忆是必需的。
影响因子：
16.2
作者：
Kim YJ;Khoshkhoo S;Frankowski JC;Zhu B;Abbasi S;Lee S;Wu YE;Hunt RF
通讯作者：
Hunt RF
DOI：
10.1016/j.jalz.2016.12.012
发表时间：
2017-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Jun GR;Chung J;Mez J;Barber R;Beecham GW;Bennett DA;Buxbaum JD;Byrd GS;Carrasquillo MM;Crane PK;Cruchaga C;De Jager P;Ertekin-Taner N;Evans D;Fallin MD;Foroud TM;Friedland RP;Goate AM;Graff-Radford NR;Hendrie H;Hall KS;Hamilton-Nelson KL;Inzelberg R;Kamboh MI;Kauwe JSK;Kukull WA;Kunkle BW;Kuwano R;Larson EB;Logue MW;Manly JJ;Martin ER;Montine TJ;Mukherjee S;Naj A;Reiman EM;Reitz C;Sherva R;St George-Hyslop PH;Thornton T;Younkin SG;Vardarajan BN;Wang LS;Wendlund JR;Winslow AR;Alzheimer's Disease Genetics Consortium;Haines J;Mayeux R;Pericak-Vance MA;Schellenberg G;Lunetta KL;Farrer LA
通讯作者：
Farrer LA
影响因子：
3.7
作者：
Miyashita A;Koike A;Jun G;Wang LS;Takahashi S;Matsubara E;Kawarabayashi T;Shoji M;Tomita N;Arai H;Asada T;Harigaya Y;Ikeda M;Amari M;Hanyu H;Higuchi S;Ikeuchi T;Nishizawa M;Suga M;Kawase Y;Akatsu H;Kosaka K;Yamamoto T;Imagawa M;Hamaguchi T;Yamada M;Morihara T;Takeda M;Takao T;Nakata K;Fujisawa Y;Sasaki K;Watanabe K;Nakashima K;Urakami K;Ooya T;Takahashi M;Yuzuriha T;Serikawa K;Yoshimoto S;Nakagawa R;Kim JW;Ki CS;Won HH;Na DL;Seo SW;Mook-Jung I;Alzheimer Disease Genetics Consortium;St George-Hyslop P;Mayeux R;Haines JL;Pericak-Vance MA;Yoshida M;Nishida N;Tokunaga K;Yamamoto K;Tsuji S;Kanazawa I;Ihara Y;Schellenberg GD;Farrer LA;Kuwano R
通讯作者：
Kuwano R
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.8
作者：
Meng, Y;Baldwin, CT;Farrer, LA
通讯作者：
Farrer, LA