Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.
Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.
复制标题
全基因组对言语记忆的言论性记忆的研究：基因组流行病学财团的心脏和衰老研究的同龄人。
DOI：
10.1016/j.biopsych.2014.08.027
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发表时间：
2015-04-15
影响因子：
10.6
通讯作者：
Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
中科院分区：
文献类型：
--
作者：
Debette S;Ibrahim Verbaas CA;Bressler J;Schuur M;Smith A;Bis JC;Davies G;Wolf C;Gudnason V;Chibnik LB;Yang Q;deStefano AL;de Quervain DJ;Srikanth V;Lahti J;Grabe HJ;Smith JA;Priebe L;Yu L;Karbalai N;Hayward C;Wilson JF;Campbell H;Petrovic K;Fornage M;Chauhan G;Yeo R;Boxall R;Becker J;Stegle O;Mather KA;Chouraki V;Sun Q;Rose LM;Resnick S;Oldmeadow C;Kirin M;Wright AF;Jonsdottir MK;Au R;Becker A;Amin N;Nalls MA;Turner ST;Kardia SL;Oostra B;Windham G;Coker LH;Zhao W;Knopman DS;Heiss G;Griswold ME;Gottesman RF;Vitart V;Hastie ND;Zgaga L;Rudan I;Polasek O;Holliday EG;Schofield P;Choi SH;Tanaka T;An Y;Perry RT;Kennedy RE;Sale MM;Wang J;Wadley VG;Liewald DC;Ridker PM;Gow AJ;Pattie A;Starr JM;Porteous D;Liu X;Thomson R;Armstrong NJ;Eiriksdottir G;Assareh AA;Kochan NA;Widen E;Palotie A;Hsieh YC;Eriksson JG;Vogler C;van Swieten JC;Shulman JM;Beiser A;Rotter J;Schmidt CO;Hoffmann W;Nöthen MM;Ferrucci L;Attia J;Uitterlinden AG;Amouyel P;Dartigues JF;Amieva H;Räikkönen K;Garcia M;Wolf PA;Hofman A;Longstreth WT Jr;Psaty BM;Boerwinkle E;DeJager PL;Sachdev PS;Schmidt R;Breteler MM;Teumer A;Lopez OL;Cichon S;Chasman DI;Grodstein F;Müller-Myhsok B;Tzourio C;Papassotiropoulos A;Bennett DA;Ikram MA;Deary IJ;van Duijn CM;Launer L;Fitzpatrick AL;Seshadri S;Mosley TH Jr;Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium
老年人的记忆表现可以反映出遗传对认知功能和痴呆过程的影响。我们的目的是确定遗传贡献的口头陈述性记忆在社区设置。我们在基因组流行病学联盟心脏和衰老研究队列的19个队列中进行了段落或单词列表延迟回忆的全基因组关联研究，这些队列包括29，076名年龄≥45岁的欧洲血统的无痴呆和中风个体。在10，617名欧洲血统的参与者，3811名非洲裔美国人和1561名年轻人中寻找暗示性关联的复制（p < 5 × 10−6）。在发现队列（p = 5.57 × 10−10）和复制队列（p = 5.65 × 10−8）中，接近APOE的rs4420638与延迟回忆表现较差相关。这种关联是更强的段落比单词列表延迟回忆和最古老的人。在总样本的子集中，与特异性测试的两种关联在发现和复制的联合分析中达到了全基因组显著性（rs11074779 [HS3ST 4]，p = 3.11 × 10−8，和rs6813517 [SPOCK 3]，p = 2.58 × 10−8），靠近参与免疫反应的基因。在725个尸检样本中，结合58个独立的提示性记忆风险变异的遗传评分与阿尔茨海默病病理学的增加相关。在138个人类海马样本中，记忆风险位点与基因表达的关联显示与WDR48和CLDN5的顺式关联，两者都与泛素代谢有关。这项迄今为止规模最大的研究探索了约40，000名老年人记忆功能的遗传学，揭示了全基因组的关联，并表明免疫和泛素途径的参与。
Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia-and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10−6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10−10) and replication cohorts (p = 5.65 × 10−8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10−8, and rs6813517 [SPOCK3], p = 2.58 × 10−8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. This largest study to date exploring the genetics of memory function in ~ 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.