Impact of neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia

David Chandler, Milan Dragovic, Matthew Cooper, Johanna Badcock, Benjamin Mullin, Deborah Faulkner, Scott Wilson, J. Hallmayer, S. Howell, Danny Rock, Lyle Palmer, Luba Kalaydjieva, Assen Jablensky

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Abstract

Neuritin 1 (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P = 0.024 and P = 0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rs1475157–rs9405890 haplotypes revealed a highly significant association with the abstraction component of current (“fluid”) intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of “fluid” intelligence.
Original languageEnglish
Pages (from-to)428-437
JournalAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume153B
Issue number2
DOIs
Publication statusPublished - 2010

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Intelligence
Schizophrenia
Single Nucleotide Polymorphism
Regression Analysis
Chromosomes, Human, Pair 6
Neuronal Plasticity
Aptitude
Haplotypes
Linear Models
Logistic Models
Maintenance
Control Groups
Genes

Cite this

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title = "Impact of neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia",
abstract = "Neuritin 1 (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P = 0.024 and P = 0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rs1475157–rs9405890 haplotypes revealed a highly significant association with the abstraction component of current (“fluid”) intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of “fluid” intelligence.",
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Impact of neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia. / Chandler, David; Dragovic, Milan; Cooper, Matthew; Badcock, Johanna; Mullin, Benjamin; Faulkner, Deborah; Wilson, Scott; Hallmayer, J.; Howell, S.; Rock, Danny; Palmer, Lyle; Kalaydjieva, Luba; Jablensky, Assen.

In: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Vol. 153B, No. 2, 2010, p. 428-437.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Impact of neuritin 1 (NRN1) polymorphisms on fluid intelligence in schizophrenia

AU - Chandler, David

AU - Dragovic, Milan

AU - Cooper, Matthew

AU - Badcock, Johanna

AU - Mullin, Benjamin

AU - Faulkner, Deborah

AU - Wilson, Scott

AU - Hallmayer, J.

AU - Howell, S.

AU - Rock, Danny

AU - Palmer, Lyle

AU - Kalaydjieva, Luba

AU - Jablensky, Assen

PY - 2010

Y1 - 2010

N2 - Neuritin 1 (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P = 0.024 and P = 0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rs1475157–rs9405890 haplotypes revealed a highly significant association with the abstraction component of current (“fluid”) intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of “fluid” intelligence.

AB - Neuritin 1 (NRN1), an activity-regulated gene with multiple roles in neurodevelopment and synaptic plasticity, is located within the 6p24-p25 interval on chromosome 6, previously identified as linked to a subtype of schizophrenia (SZ) characterized by pervasive cognitive deficit (CD). We have tested the effect of NRN1 sequence variation on susceptibility to SZ and on general cognitive ability in patients and non-psychiatric control subjects by re-sequencing the coding regions of NRN1 and its flanking sequences, and genotyping 19 single-nucleotide polymorphisms (SNPs) in 336 SZ patients and 172 healthy control individuals. All participants completed comprehensive neurocognitive assessment, including tests estimating premorbid/prior IQ and current IQ. Logistic regression analyses found no significant association for any of the 19 SNPs with SZ or its CD subtype. However, linear regression analysis gave significant association (P = 0.024 and P = 0.027 after correction for multiple testing) for polymorphisms rs1475157 and rs9405890 with current IQ in the patient group. In SZ, the rs1475157–rs9405890 haplotypes revealed a highly significant association with the abstraction component of current (“fluid”) intelligence (P = 0.0014), and with percentage loss of IQ points between premorbid and current intelligence (P = 0.0041). Results in the control group were not significant after correction. This is the first analysis of association between variation in NRN1 and SZ. The findings suggest a role of NRN1 as a modifier of cognitive functioning in SZ, with implications for future research into the impact of the environment on the development and maintenance of “fluid” intelligence.

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DO - 10.1002/ajmg.b.30996

M3 - Article

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SP - 428

EP - 437

JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics

SN - 1552-4841

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