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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
Molecular Psychiatry ( IF 9.6 ) Pub Date : 2022-08-16 , DOI: 10.1038/s41380-022-01710-8
Jari Lahti 1, 2 , Samuli Tuominen 1 , Qiong Yang 3 , Giulio Pergola 4, 5 , Shahzad Ahmad 6 , Najaf Amin 6 , Nicola J Armstrong 7 , Alexa Beiser 3, 8 , Katharina Bey 9, 10 , Joshua C Bis 11 , Eric Boerwinkle 12, 13 , Jan Bressler 12 , Archie Campbell 14, 15 , Harry Campbell 16 , Qiang Chen 4 , Janie Corley 17 , Simon R Cox 17 , Gail Davies 17 , Philip L De Jager 18 , Eske M Derks 19 , Jessica D Faul 20 , Annette L Fitzpatrick 21, 22, 23 , Alison E Fohner 22, 24 , Ian Ford 25 , Myriam Fornage 26 , Zachary Gerring 19 , Hans J Grabe 27, 28 , Francine Grodstein 29, 30 , Vilmundur Gudnason 31, 32 , Eleanor Simonsick 33 , Elizabeth G Holliday 34 , Peter K Joshi 16, 35 , Eero Kajantie 36, 37, 38 , Jaakko Kaprio 39, 40 , Pauliina Karell 39 , Luca Kleineidam 10, 41 , Maria J Knol 6 , Nicole A Kochan 42, 43 , John B Kwok 44, 45 , Markus Leber 46 , Max Lam 47, 48 , Teresa Lee 42, 43 , Shuo Li 3 , Anu Loukola 49 , Tobias Luck 50, 51, 52 , Riccardo E Marioni 14, 53 , Karen A Mather 42, 54 , Sarah Medland 55 , Saira S Mirza 6, 56 , Mike A Nalls 57, 58 , Kwangsik Nho 59, 60, 61 , Adrienne O'Donnell 3, 8 , Christopher Oldmeadow 62 , Jodie Painter 55 , Alison Pattie 17 , Simone Reppermund 42, 63 , Shannon L Risacher 59, 61 , Richard J Rose 64 , Vijay Sadashivaiah 4 , Markus Scholz 65, 66 , Claudia L Satizabal 8, 67, 68 , Peter W Schofield 69 , Katharina E Schraut 16, 70 , Rodney J Scott 71, 72 , Jeannette Simino 73 , Albert V Smith 31, 32 , Jennifer A Smith 74, 75 , David J Stott 76 , Ida Surakka 77 , Alexander Teumer 78 , Anbupalam Thalamuthu 42 , Stella Trompet 79 , Stephen T Turner 80 , Sven J van der Lee 6, 81 , Arno Villringer 82, 83 , Uwe Völker 84 , Robert S Wilson 85 , Katharina Wittfeld 27, 28 , Eero Vuoksimaa 39 , Rui Xia 86 , Kristine Yaffe 87 , Lei Yu 85 , Habil Zare 88, 89, 90 , Wei Zhao 74 , David Ames 91, 92 , John Attia 34, 62 , David A Bennett 85 , Henry Brodaty 42, 93 , Daniel I Chasman 94, 95 , Aaron L Goldman 4 , Caroline Hayward 96 , M Arfan Ikram 6 , J Wouter Jukema 97 , Sharon L R Kardia 74 , Todd Lencz 98 , Markus Loeffler 65, 66 , Venkata S Mattay 4, 99 , Aarno Palotie 39, 100, 101 , Bruce M Psaty 11, 102, 103 , Alfredo Ramirez 41, 46 , Paul M Ridker 94, 95 , Steffi G Riedel-Heller 104 , Perminder S Sachdev 42, 43 , Andrew J Saykin 59, 60, 61 , Martin Scherer 105 , Peter R Schofield 45, 106 , Stephen Sidney 107 , John M Starr 17, 108 , Julian Trollor 42, 109 , William Ulrich 4 , Michael Wagner 10, 41 , David R Weir 20 , James F Wilson 16, 96 , Margaret J Wright 110, 111 , Daniel R Weinberger 4, 112, 113, 114 , Stephanie Debette 115, 116 , Johan G Eriksson 117, 118, 119 , Thomas H Mosley 120 , Lenore J Launer 121 , Cornelia M van Duijn 6, 122 , Ian J Deary 17, 53 , Sudha Seshadri 8, 67, 68 , Katri Räikkönen 1
Affiliation  

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.



中文翻译:


全基因组荟萃分析揭示了言语短期记忆和学习的新位点



了解记忆过程的基因组基础可能有助于对抗神经退行性疾病。因此,我们在没有痴呆或中风的成年人中研究了常见遗传变异与言语短期记忆和言语学习的关联( N = 53,637)。我们在CDH18的内含子区域以及 13q21 和 3p21.1 处鉴定了新的位点,以及APOE/APOC1/TOMM40区域中的预期信号。这些结果在独立样本中得到重复。功能和生物信息学分析支持其中许多位点并进一步暗示POC1 。我们表明,言语学习的多基因评分与工作记忆任务期间右顶枕区的大脑激活相关。最后,我们展示了这些记忆特征与几种神经认知和健康结果的遗传相关性。我们的研究结果表明了几个基因组位点在言语记忆过程中的作用。

更新日期:2022-08-16
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