Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.
Genetic variants specific to aging-related verbal memory: Insights from GWASs in a population-based cohort.
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DOI：
10.1371/journal.pone.0182448
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Prescott CA
中科院分区：
文献类型：
--
作者：
Arpawong TE;Pendleton N;Mekli K;McArdle JJ;Gatz M;Armoskus C;Knowles JA;Prescott CA
言语记忆通常使用立即回忆 (IR) 和延迟回忆 (DR) 分数来研究，尽管 DR 取决于 IR 能力。分离这些成分可能有助于破译与年龄相关的记忆能力的遗传变异。本研究的目的是 (a) 构建老年期 IR 和延迟回忆或残留 DR (rDR) 独立方面的个体轨迹； (b) 确定有助于四种估计表型的遗传标记：IR 和 rDR 水平以及 60 岁后的变化。认知完整样本（N = 20,650，125,164 个观察值）取自美国健康与退休研究，这是一项针对 50 岁及以上成年人的全国代表性研究。使用每两年（1996-2012）收集的数据重复测量构建混合效应回归模型，以估计 IR 和 rDR 60 岁时的水平以及 60 岁后的记忆变化。使用约 120 万个单核苷酸多态性 (SNP) 在基因型子样本 (N = 7,486) 中进行全基因组关联扫描 (GWAS)。 TOMM40 中的一个 SNP (rs2075650) 与全基因组水平的 rDR 水平相关 (p = 5.0x10-08)，这一效应在英国衰老纵向研究的独立样本中得到了复制（N = 6,898，有 41,328 个观察值）。 rDR 水平的荟萃分析证实了这种关联 (p = 5.0x10-11)，并在 TOMM40 中确定了另外两个 (rs71352238 p = 1.0x10-10；rs157582 p = 7.0x10-09)，以及 APOE 中的一个 (rs769449 p = 3.1 x10-12)。 IR 变化的荟萃分析确定了与 TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) 和 APOE (rs769449 p = 2.2x10-08) 中三个相同 SNP 的关联。条件分析表明，rDR 水平上的 GWAS 信号由 APOE 驱动，而 IR 变化信号由 TOMM40 驱动。此外，我们发现 TOMM40 对两种表型的影响均独立于 APOE e4。这是美国第一项针对与年龄相关的即时和延迟言语记忆进行的基于人群的 GWAS 研究的结果，值得继续对其他样本和言语记忆的额外测量进行检查。
Verbal memory is typically studied using immediate recall (IR) and delayed recall (DR) scores, although DR is dependent on IR capability. Separating these components may be useful for deciphering the genetic variation in age-related memory abilities. This study was conducted to (a) construct individual trajectories in IR and independent aspects of delayed recall, or residualized-DR (rDR), across older adulthood; and (b) identify genetic markers that contribute to four estimated phenotypes: IR and rDR levels and changes after age 60. A cognitively intact sample (N = 20,650 with 125,164 observations) was drawn from the U.S. Health and Retirement Study, a nationally representative study of adults aged 50 and older. Mixed effects regression models were constructed using repeated measures from data collected every two years (1996–2012) to estimate level at age 60 and change in memory post-60 in IR and rDR. Genome-wide association scans (GWAS) were conducted in the genotypic subsample (N = 7,486) using ~1.2 million single nucleotide polymorphisms (SNPs). One SNP (rs2075650) in TOMM40 associated with rDR level at the genome-wide level (p = 5.0x10-08), an effect that replicated in an independent sample from the English Longitudinal Study on Ageing (N = 6,898 with 41,328 observations). Meta-analysis of rDR level confirmed the association (p = 5.0x10-11) and identified two others in TOMM40 (rs71352238 p = 1.0x10-10; rs157582 p = 7.0x10-09), and one in APOE (rs769449 p = 3.1 x10-12). Meta-analysis of IR change identified associations with three of the same SNPs in TOMM40 (rs157582 p = 8.3x10-10; rs71352238 p = 1.9x10-09) and APOE (rs769449 p = 2.2x10-08). Conditional analyses indicate GWAS signals on rDR level were driven by APOE, whereas signals on IR change were driven by TOMM40. Additionally, we found that TOMM40 had effects independent of APOE e4 on both phenotypes. Findings from this first U.S. population-based GWAS study conducted on both age-related immediate and delayed verbal memory merit continued examination in other samples and additional measures of verbal memory.
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影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
--
作者：
Gomar, Jesus J.;Bobes-Bascaran, Maria T.;Goldberg, Terry E.
通讯作者：
Goldberg, Terry E.
影响因子：
2.1
作者：
Bacanu, SA;Devlin, B;Roeder, K
通讯作者：
Roeder, K
影响因子：
2.5
作者：
Helmstaedter, C;Grunwald, T;Elger, CE
通讯作者：
Elger, CE
影响因子：
2.6
作者：
Elger, CE;Grunwald, T;Heinze, HJ
通讯作者：
Heinze, HJ