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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

ABSTRACT: 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.

SUBMITTER: Lahti J

PROVIDER: S-EPMC9734053 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

Lahti Jari J Tuominen Samuli S Yang Qiong Q Pergola Giulio G Ahmad Shahzad S Amin Najaf N Armstrong Nicola J NJ Beiser Alexa A Bey Katharina K Bis Joshua C JC Boerwinkle Eric E Bressler Jan J Campbell Archie A Campbell Harry H Chen Qiang Q Corley Janie J Cox Simon R SR Davies Gail G De Jager Philip L PL Derks Eske M EM Faul Jessica D JD Fitzpatrick Annette L AL Fohner Alison E AE Ford Ian I Fornage Myriam M Gerring Zachary Z Grabe Hans J HJ Grodstein Francine F Gudnason Vilmundur V Simonsick Eleanor E Holliday Elizabeth G EG Joshi Peter K PK Kajantie Eero E Kaprio Jaakko J Karell Pauliina P Kleineidam Luca L Knol Maria J MJ Kochan Nicole A NA Kwok John B JB Leber Markus M Lam Max M Lee Teresa T Li Shuo S Loukola Anu A Luck Tobias T Marioni Riccardo E RE Mather Karen A KA Medland Sarah S Mirza Saira S SS Nalls Mike A MA Nho Kwangsik K O'Donnell Adrienne A Oldmeadow Christopher C Painter Jodie J Pattie Alison A Reppermund Simone S Risacher Shannon L SL Rose Richard J RJ Sadashivaiah Vijay V Scholz Markus M Satizabal Claudia L CL Schofield Peter W PW Schraut Katharina E KE Scott Rodney J RJ Simino Jeannette J Smith Albert V AV Smith Jennifer A JA Stott David J DJ Surakka Ida I Teumer Alexander A Thalamuthu Anbupalam A Trompet Stella S Turner Stephen T ST van der Lee Sven J SJ Villringer Arno A Völker Uwe U Wilson Robert S RS Wittfeld Katharina K Vuoksimaa Eero E Xia Rui R Yaffe Kristine K Yu Lei L Zare Habil H Zhao Wei W Ames David D Attia John J Bennett David A DA Brodaty Henry H Chasman Daniel I DI Goldman Aaron L AL Hayward Caroline C Ikram M Arfan MA Jukema J Wouter JW Kardia Sharon L R SLR Lencz Todd T Loeffler Markus M Mattay Venkata S VS Palotie Aarno A Psaty Bruce M BM Ramirez Alfredo A Ridker Paul M PM Riedel-Heller Steffi G SG Sachdev Perminder S PS Saykin Andrew J AJ Scherer Martin M Schofield Peter R PR Sidney Stephen S Starr John M JM Trollor Julian J Ulrich William W Wagner Michael M Weir David R DR Wilson James F JF Wright Margaret J MJ Weinberger Daniel R DR Debette Stephanie S Eriksson Johan G JG Mosley Thomas H TH Launer Lenore J LJ van Duijn Cornelia M CM Deary Ian J IJ Seshadri Sudha S Räikkönen Katri K

Molecular psychiatry 20220816 11

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 analyse ...[more]

PMID: 35974141

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Project description:Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of functional independence or modularity exists in this distributed anatomical-cognitive system.

Dataset Information

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

Publications

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

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