A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains

被引：50

作者：

Ranlund, Siri ^{[1
,2
,3
]}

Calafato, Stella ^{[1
]}

Thygesen, Johan H. ^{[1
]}

Lin, Kuang ^{[2
,3
,4
]}

Cahn, Wiepke ^{[5
]}

Crespo-Facorro, Benedicto ^{[6
,7
]}

de Zwarte, Sonja M. C. ^{[5
]}

Diez, Alvaro ^{[1
,8
,9
]}

Di Forti, Marta ^{[2
,3
]}

Iyegbe, Conrad ^{[2
,3
]}

Jablensky, Assen ^{[10
]}

Jones, Rebecca ^{[1
]}

Hall, Mei-Hua ^{[11
]}

Kahn, Rene ^{[5
]}

Kalaydjieva, Luba ^{[12
,13
]}

Kravariti, Eugenia ^{[2
,3
]}

McDonald, Colm ^{[14
,15
]}

McIntosh, Andrew M. ^{[16
,17
]}

McQuillin, Andrew ^{[1
]}

Picchioni, Marco ^{[2
,3
]}

Prata, Diana P. ^{[2
,3
,18
]}

Rujescu, Dan ^{[19
,20
]}

Schulze, Katja ^{[2
,3
]}

Shaikh, Madiha ^{[21
,22
]}

Toulopoulou, Timothea ^{[2
,3
,23
,24
,25
]}

van Haren, Neeltje ^{[5
]}

van Os, Jim ^{[2
,3
,26
]}

Vassos, Evangelos ^{[2
,3
]}

Walshe, Muriel ^{[1
,2
,3
]}

Lewis, Cathryn ^{[2
,3
]}

Murray, Robin M. ^{[2
,3
]}

Powell, John ^{[2
,3
]}

Bramon, Elvira ^{[1
,2
,3
,27
]}

机构：

[1] UCL, Div Psychiat, London, England

[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England

[3] South London Maudsley NHS Fdn Trust, London, England

[4] Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England

[5] Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands

[6] Ctr Invest Biomed Red Salud Mental, CIBERSAM, Madrid, Spain

[7] Univ Cantabria IDIVAL, Univ Hosp Marques de Valdecilla, Sch Med, Dept Psychiat, Santander, Spain

[8] Univ Complutense Madrid, Lab Cognit & Computat Neurosci, Ctr Biomed Technol CTB, Madrid, Spain

[9] Tech Univ Madrid, Madrid, Spain

[10] Univ Western Australia, Ctr Clin Res Neuropsychiat, Perth, WA, Australia

[11] Harvard Med Sch, McLean Hosp, Psychosis Neurobiol Lab, Belmont, MA USA

[12] Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA, Australia

[13] Univ Western Australia, Med Res Ctr, Perth, WA, Australia

[14] Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, Galway, Ireland

[15] Natl Univ Ireland Galway, NCBES Galway Neurosci Ctr, Galway, Ireland

[16] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland

[17] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[18] Univ Lisbon, Inst Med Mol, Fac Med, Lisbon, Portugal

[19] Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany

[20] Univ Halle Wittenberg, Dept Psychiat Psychotherapy & Psychosomat, Halle, Germany

[21] North East London Fdn Trust, London, England

[22] UCL, Res Dept Clin Educ & Hlth Psychol, London, England

[23] Bilkent Univ, Dept Psychol, Main Campus, Ankara, Turkey

[24] Univ Hong Kong, Dept Psychol, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China

[25] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong Jockey Club Bldg Interdisciplinary Res, Hong Kong, Hong Kong, Peoples R China

[26] Maastricht Univ, Dept Psychiat & Psychol, EURON, Med Ctr, Maastricht, Netherlands

[27] UCL, Inst Cognit Neurosci, London, England

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2018年 / 177卷 / 01期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

bipolar disorder; cognition; EEG; schizophrenia; single nucleotide polymorphism (SNP); UNAFFECTED 1ST-DEGREE RELATIVES; WIDE ASSOCIATION ANALYSIS; BIPOLAR DISORDER; WORKING-MEMORY; GENETIC OVERLAP; WHITE-MATTER; PSYCHOPHYSIOLOGICAL ENDOPHENOTYPES; 1ST-EPISODE SCHIZOPHRENIA; INTERMEDIATE PHENOTYPES; PSYCHIATRIC-DISORDERS;

D O I：

10.1002/ajmg.b.32581

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N=515), lateral ventricular volume (N=798), and the cognitive measures block design (N=3,089), digit span (N=1,437), and the Ray Auditory Verbal Learning Task (N=2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p=0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p=0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p=0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.

引用

页码：21 / 34

页数：14

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