Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-18T18:47:18.676Z Has data issue: false hasContentIssue false
  • English
  • Français

Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Published online by Cambridge University Press:  04 March 2018

Valentina Escott-Price Open the ORCID record for Valentina Escott-Price [Opens in a new window] ,
Daniel J. Smith ,
Kimberley Kendall ,
Joey Ward ,
George Kirov ,
Michael J. Owen ,
James Walters  and
Michael C. O'Donovan
Valentina Escott-Price*
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Daniel J. Smith
Affiliation:
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Kimberley Kendall
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Joey Ward
Affiliation:
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
George Kirov
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Michael J. Owen
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
James Walters
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Michael C. O'Donovan
Affiliation:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
*
Author for correspondence: Valentina Escott-Price, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.

Methods

Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.

Results

Neither genetic measure was associated with season or month of birth within the UKBB sample.

Conclusions

As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.

Keywords

Polygenic risk scoreschizophreniaseason of birth
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 15 , November 2019 , pp. 2499 - 2504
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Adan, A, Arredondo, AY, Capella, MD, Prat, G, Forero, DA and Navarro, JF (2017) Neurobiological underpinnings and modulating factors in schizophrenia spectrum disorders with a comorbid substance use disorder: a systematic review. Neuroscience & Biobehavioral Reviews 75, 361–377.Google Scholar
Baron, M and Gruen, R (1988) Risk factors in schizophrenia. Season of birth and family history. British Journal of Psychiatry, 152, 460–465.Google Scholar
Boyd, JH, Pulver, AE and Stewart, W (1986) Season of birth: schizophrenia and bipolar disorder. Schizophrenia Bulletin 12(2), 173–186.Google Scholar
Bradbury, TN and Miller, GA (1985) Season of birth in schizophrenia: a review of evidence, methodology, and etiology. Psychological Bulletin, 98(3), 569–594.Google Scholar
Bulik-Sullivan, BK, Loh, PR, Finucane, HK, Ripke, S, Yang, J, Schizophrenia Working Group of the PGC, Patterson, N et al. (2015) LD score regression distinguishes confounding from polygenicity in genome-wide association studies. Nature Genetics 47(3), 291–295.Google Scholar
Byrne, EM, Psychiatric Genetics Consortium Major Depressive Disorder Working Group, Raheja, UK, Stephens, SH, Heath, AC, Madden, PA, Vaswani, D et al. (2015) Seasonality shows evidence for polygenic architecture and genetic correlation with schizophrenia and bipolar disorder. Journal of Clinical Psychiatry 76(2), 128–134.Google Scholar
Cardno, AG and Gottesman, II (2000) Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. American Journal of Medical Genetics 97(1), 12–17.Google Scholar
Coe, BP, Witherspoon, K, Rosenfeld, JA, van Bon, BW, Vulto-van Silfhout, AT, Bosco, P et al. (2014) Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nature Genetics 46(10), 1063–1071.Google Scholar
Davies, G, Welham, J, Chant, D, Torrey, EF and McGrath, J (2003) A systematic review and meta-analysis of northern hemisphere season of birth studies in schizophrenia. Schizophrenia Bulletin 29(3), 587–593.Google Scholar
Delaneau, O, Zagury, JF and Marchini, J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nature Methods 10(1), 5–6.Google Scholar
Devlin, B and Roeder, K (1999) Genomic control for association studies. Biometrics 55(4), 997–1004.Google Scholar
Disanto, G, Morahan, JM, Lacey, MV, DeLuca, GC, Giovannoni, G, Ebers, GC et al. (2012) Seasonal distribution of psychiatric births in England. PLoS ONE 7(4), e34866.Google Scholar
Dittwald, P, Gambin, T, Szafranski, P, Li, J, Amato, S, Divon, MY et al. (2013) NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits. Genome Research 23(9), 1395–1409.Google Scholar
Dudbridge, F (2013) Power and predictive accuracy of polygenic risk scores. PLoS Genetics 9(3), e1003348.Google Scholar
Ellman, LM, Huttunen, M, Lonnqvist, J and Cannon, TD (2007) The effects of genetic liability for schizophrenia and maternal smoking during pregnancy on obstetric complications. Schizophrenia Research 93(1–3), 229–236.Google Scholar
Grootendorst-van Mil, NH, Steegers-Theunissen, RPM, Hofman, A, Jaddoe, VWV, Verhulst, FC and Tiemeier, H (2017) Brighter children? The association between seasonality of birth and child IQ in a population-based birth cohort. BMJ Open 7, e012406. doi:10.1136/bmjopen-2016-012406.Google Scholar
Hettema, JM, Walsh, D and Kendler, KS (1996) Testing the effect of season of birth on familial risk for schizophrenia and related disorders, British Journal of Psychiatry 168(2), 205–209.Google Scholar
Howie, B, Fuchsberger, C, Stephens, M, Marchini, J and Abecasis, GR (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nature Genetics 44(8), 955–959.Google Scholar
International Schizophrenia Consortium, Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF et al. (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460(7256), 748–752.Google Scholar
Jeronimus, BF, Stavrakakis, N, Veenstra, R and Oldehinkel, AJ (2015) Relative Age effects in Dutch adolescents: concurrent and prospective analyses. PLoS ONE 10(6), e0128856.Google Scholar
Kendall, KM, Rees, E, Escott-Price, V, Einon, M, Thomas, R, Hewitt, J et al. (2017) Cognitive performance Among carriers of pathogenic copy number variants: analysis of 152000 UK biobank subjects. Biological Psychiatry 82(2), 103–110.Google Scholar
McGrath, J (1999) Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophrenia Research 40(3), 173–177.Google Scholar
Mortensen, PB, Pedersen, CB, Westergaard, T, Wohlfahrt, J, Ewald, H, Mors, O et al. (1999) Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340(8), 603–608.Google Scholar
Natale, V and Adan, A (1999) Season of birth modulates morningness-eveningness preference in humans. Neuroscience Letter 274(2), 139–141.Google Scholar
Natale, V, Adan, A and Fabbri, M (2009) Season of birth, gender, and social-cultural effects on sleep timing preferences in humans. Sleep 32(3), 423–426.Google Scholar
Pardiñas, AF, Holmans, P, Pocklington, AJ, Escott-Price, V, Ripke, S, Carrera, N, et al. (2018) Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection. Nature Genetics, (in press). http://dx.doi.org/10.1038/s41588-018-0059-2.Google Scholar
Power, RA, Verweij, KJ, Zuhair, M, Montgomery, GW, Henders, AK, Heath, AC et al. (2014) Genetic predisposition to schizophrenia associated with increased use of cannabis. Molecular Psychiatry 19(11), 1201–1204.Google Scholar
Purcell, SM, Moran, JL, Fromer, M, Ruderfer, D, Solovieff, N, Roussos, P et al. (2014) A polygenic burden of rare disruptive mutations in schizophrenia. Nature 506(7487), 185–190.Google Scholar
Rees, E, Walters, JT, Georgieva, L, Isles, AR, Chambert, KD, Richards, AL et al. (2014) Analysis of copy number variations at 15 schizophrenia-associated loci. British Journal of Psychiatry 204(2), 108–114.Google Scholar
Ripke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kahler, AK, Akterin, S, et al. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics 45(10), 1150–1159.Google Scholar
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510), 421–427.Google Scholar
Singh, T, Kurki, MI, Curtis, D, Purcell, SM, Crooks, L, McRae, J et al. (2016) Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders, Nature Neuroscience 19(4), 571–577.Google Scholar
Smith, DJ, Escott-Price, V, Davies, G, Bailey, ME, Colodro-Conde, L, Ward, J et al. (2016) Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci. Molecular Psychiatry 21(6), 749–757.Google Scholar
Sudlow, C, Gallacher, J, Allen, N, Beral, V, Burton, P, Danesh, J et al. (2015) UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Medicine 12(3), e1001779.Google Scholar
Sullivan, PF, Kendler, KS and Neale, MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60(12), 1187–1192.Google Scholar
Suvisaari, JM, Haukka, JK and Lonnqvist, JK (2004) No association between season of birth of patients with schizophrenia and risk of schizophrenia among their siblings, Schizophrenia Research 66(1), 1–6.Google Scholar
Svensson, AC, Lichtenstein, P, Sandin, S, Oberg, S, Sullivan, PF and Hultman, CM (2012) Familial aggregation of schizophrenia: the moderating effect of age at onset, parental immigration, paternal age and season of birth. Scandinavial Journal Public Health 40(1), 43–50.Google Scholar
Thapar, A, Rice, F, Hay, D, Boivin, J, Langley, K, van den Bree, M et al. (2009) Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biological Psychiatry 66(8), 722–727.Google Scholar
Torrey, EF, Torrey, BB and Peterson, MR (1977) Seasonality of schizophrenic births in the United States. Archives General Psychiatry 34(9), 1065–1070.Google Scholar
Vaucher, J, Keating, BJ, Lasserr, AM, Gan, W, Lyall, DM, Ward, J et al. (2017) Cannabis use and risk of schizophrenia: a Mendelian randomization study. Molecular Psychiatry doi: 10.1038/mp.2016.252.Google Scholar
Supplementary material: File

Escott-Price et al. supplementary material

Table S1 and Figures S1-S2

Download Escott-Price et al. supplementary material(File)
File 106.3 KB