A genetic association study of CSMD1 and CSMD2 with cognitive function

被引：50

作者：

Athanasiu, Lavinia ^{[1
,2
]}

Giddaluru, Sudheer ^{[4
,5
]}

Fernandes, Carla ^{[4
,5
]}

Christoforou, Andrea ^{[4
,5
]}

Reinvang, Ivar ^{[6
]}

Lundervold, Astri J. ^{[7
,8
]}

Nilsson, Lars-Goran ^{[9
,10
]}

Kauppi, Karolina ^{[9
,11
]}

Adolfsson, Rolf ^{[12
]}

Eriksson, Elias ^{[13
]}

Sundet, Kjetil ^{[6
]}

Djurovic, Srdjan ^{[2
,3
,4
]}

Espeseth, Thomas ^{[1
,6
]}

Nyberg, Lars ^{[9
,11
,14
]}

Steen, Vidar M. ^{[4
,5
]}

Andreassen, Ole A. ^{[2
,3
]}

Le Hellard, Stephanie ^{[4
,5
]}

机构：

[1] Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr Psychosis Res, N-0407 Oslo, Norway

[2] Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr Psychosis Res, N-0407 Oslo, Norway

[3] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway

[4] Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5021 Bergen, Norway

[5] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway

[6] Univ Oslo, Dept Psychol, Oslo, Norway

[7] Dept Biol & Med Psychol, Jonas Lies Vei 91, Bergen, Norway

[8] Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, N-5009 Bergen, Norway

[9] Umea Univ, Umea Ctr Funct Brain Imaging UFBI, S-90187 Umea, Sweden

[10] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden

[11] Umea Univ, Dept Integrat Med Biol, S-90187 Umea, Sweden

[12] Umea Univ, Psychiat, Dept Clin Sci, SE-90185 Umea, Sweden

[13] Gothenburg Univ, Sahlgrenska Acad, Inst Physiol & Neurosci, Dept Pharmacol, SE-40530 Gothenburg, Sweden

[14] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden

来源：

BRAIN BEHAVIOR AND IMMUNITY | 2017年 / 61卷

关键词：

Complement; Immunity; CSMD1; CSMD2; Schizophrenia; Cognition; Psychiatry; Memory; GWAS; GENOME-WIDE ASSOCIATION; RISK VARIANT RS10503253; SCHIZOPHRENIA RISK; BIPOLAR DISORDER; EXECUTIVE FUNCTION; MENTAL-DISORDERS; TEST BATTERIES; DISEASE; METAANALYSIS; BRAIN;

D O I：

10.1016/j.bbi.2016.11.026

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease. (C) 2016 The Authors. Published by Elsevier Inc.

引用

页码：209 / 216

页数：8

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