Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Baihan Wang; Olga Giannakopoulou; Isabelle Austin-zimmerman; Haritz Irizar; Jasmine Harju-seppänen; Eirini Zartaloudi; Anjali Bhat; Andrew Mcquillin; Karoline Kuchenbäcker; Elvira Bramon

doi:10.3390/genes13010106

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

Baihan Wang, Olga Giannakopoulou, Isabelle Austin-zimmerman, Haritz Irizar, Jasmine Harju-seppänen, Eirini Zartaloudi, Anjali Bhat, Andrew Mcquillin, Karoline Kuchenbäcker, Elvira Bramon

Social Genetic & Developmental Psychiatry

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

Original language	English
Article number	106
Pages (from-to)	106
Journal	Genes
Volume	13
Issue number	1
DOIs	https://doi.org/10.3390/genes13010106
Publication status	Published - 3 Jan 2022

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https://www.mdpi.com/2073-4425/13/1/106

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title = "Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample",

abstract = "Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study{\textregistered}, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.",

author = "Baihan Wang and Olga Giannakopoulou and Isabelle Austin-zimmerman and Haritz Irizar and Jasmine Harju-sepp{\"a}nen and Eirini Zartaloudi and Anjali Bhat and Andrew Mcquillin and Karoline Kuchenb{\"a}cker and Elvira Bramon",

note = "Funding Information: Funding: Baihan Wang was supported by the China Scholarship Council-University College London Joint Research Scholarship. Isabelle Austin-Zimmerman, Anjali Bhat, and Jasmine Harju-Sepp{\"a}nen were supported by the Medical Research Council doctoral studentships. Haritz Irizar has received funding from the European Union{\textquoteright}s Horizon 220 research and innovation programme under the Marie Sklodowska-Curie grant agreement no 747429 and is currently supported by a grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Elvira Bramon has received the following funding that supported this work: National Institute of Health Research UK (NIHR200756); Mental Health Research UK John Grace QC Scholarship 2018; Economic Social Research Council UK (ESRC) co-funded doctoral award. BMA Margaret Temple Fellowship 2016; Medical Research Council New Investigator and Centenary Awards (G0901310, G1100583), Medical Research Council (G1100583); Wellcome Trust awards (085475/B/08/Z, 085475/Z/08/Z) and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (UCLH BRC—Mental Health Theme). Funding Information: Acknowledgments: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study (https://abcdstudy.org; accessed on 26 November 2021), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9–10 and follow them over 10 years into early adulthood. The ABCD Study{\textregistered} is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html (accessed on 26 November 2021). A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy. org/consortium_members/ (accessed on 26 November 2021). ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from doi:10.15154/1524269. DOIs can be found at https://nda.nih.gov/abcd (accessed on 26 November 2021). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/genes13010106",

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T1 - Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

AU - Wang, Baihan

AU - Giannakopoulou, Olga

AU - Austin-zimmerman, Isabelle

AU - Irizar, Haritz

AU - Harju-seppänen, Jasmine

AU - Zartaloudi, Eirini

AU - Bhat, Anjali

AU - Mcquillin, Andrew

AU - Kuchenbäcker, Karoline

AU - Bramon, Elvira

N1 - Funding Information: Funding: Baihan Wang was supported by the China Scholarship Council-University College London Joint Research Scholarship. Isabelle Austin-Zimmerman, Anjali Bhat, and Jasmine Harju-Seppänen were supported by the Medical Research Council doctoral studentships. Haritz Irizar has received funding from the European Union’s Horizon 220 research and innovation programme under the Marie Sklodowska-Curie grant agreement no 747429 and is currently supported by a grant from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Elvira Bramon has received the following funding that supported this work: National Institute of Health Research UK (NIHR200756); Mental Health Research UK John Grace QC Scholarship 2018; Economic Social Research Council UK (ESRC) co-funded doctoral award. BMA Margaret Temple Fellowship 2016; Medical Research Council New Investigator and Centenary Awards (G0901310, G1100583), Medical Research Council (G1100583); Wellcome Trust awards (085475/B/08/Z, 085475/Z/08/Z) and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (UCLH BRC—Mental Health Theme). Funding Information: Acknowledgments: Data used in the preparation of this article were obtained from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study (https://abcdstudy.org; accessed on 26 November 2021), held in the NIMH Data Archive (NDA). This is a multisite, longitudinal study designed to recruit more than 10,000 children age 9–10 and follow them over 10 years into early adulthood. The ABCD Study® is supported by the National Institutes of Health and additional federal partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html (accessed on 26 November 2021). A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy. org/consortium_members/ (accessed on 26 November 2021). ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report came from doi:10.15154/1524269. DOIs can be found at https://nda.nih.gov/abcd (accessed on 26 November 2021). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.

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U2 - 10.3390/genes13010106

DO - 10.3390/genes13010106

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ER -

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample

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