Age at first birth in women is genetically associated with increased risk of schizophrenia

Schizophrenia Working Group of the Psychiatric Genomics Consortium; Guiyan Ni; Jacob Gratten; Naomi R. Wray; Sang Hong Lee; Esben  Agerbo; Ditte  Demontis; Thomas Hansen; Mads V. Hollegaard; David M. Hougaard; Manuel Mattheisen; Ole Mors; Line Olsen; Henrik B. Rasmussen; Anders D. Børglum; Preben B. Mortensen; Thomas Werge; Tune Hannes Pers

doi:10.1038/s41598-018-28160-z

Age at first birth in women is genetically associated with increased risk of schizophrenia

Schizophrenia Working Group of the Psychiatric Genomics Consortium, Guiyan Ni, Jacob Gratten, Naomi R. Wray, Sang Hong Lee^*, Esben Agerbo, Ditte Demontis, Thomas Hansen, Mads V. Hollegaard, David M. Hougaard, Manuel Mattheisen, Ole Mors, Line Olsen, Henrik B. Rasmussen, Anders D. Børglum, Preben B. Mortensen, Thomas Werge, Tune Hannes Pers

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Department of Health Technology

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Abstract

Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.

Original language	English
Article number	10168
Journal	Scientific Reports
Volume	8
Number of pages	14
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-018-28160-z
Publication status	Published - 2018

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Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ni, G., Gratten, J., Wray, N. R., Lee, S. H., Agerbo, E., Demontis, D., Hansen, T., Hollegaard, M. V., Hougaard, D. M., Mattheisen, M., Mors, O., Olsen, L., Rasmussen, H. B., Børglum, A. D., Mortensen, P. B., Werge, T., & Pers, T. H. (2018). Age at first birth in women is genetically associated with increased risk of schizophrenia. Scientific Reports, 8, Article 10168. https://doi.org/10.1038/s41598-018-28160-z

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title = "Age at first birth in women is genetically associated with increased risk of schizophrenia",

abstract = "Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.",

author = "{Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Guiyan Ni and Jacob Gratten and Wray, {Naomi R.} and Lee, {Sang Hong} and Esben Agerbo and Ditte Demontis and Thomas Hansen and Hollegaard, {Mads V.} and Hougaard, {David M.} and Manuel Mattheisen and Ole Mors and Line Olsen and Rasmussen, {Henrik B.} and B{\o}rglum, {Anders D.} and Mortensen, {Preben B.} and Thomas Werge and Pers, {Tune Hannes}",

year = "2018",

doi = "10.1038/s41598-018-28160-z",

language = "English",

volume = "8",

journal = "Scientific Reports",

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Schizophrenia Working Group of the Psychiatric Genomics Consortium, Ni, G, Gratten, J, Wray, NR, Lee, SH, Agerbo, E, Demontis, D, Hansen, T, Hollegaard, MV, Hougaard, DM, Mattheisen, M, Mors, O, Olsen, L, Rasmussen, HB, Børglum, AD, Mortensen, PB, Werge, T & Pers, TH 2018, 'Age at first birth in women is genetically associated with increased risk of schizophrenia', Scientific Reports, vol. 8, 10168. https://doi.org/10.1038/s41598-018-28160-z

TY - JOUR

T1 - Age at first birth in women is genetically associated with increased risk of schizophrenia

AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium

AU - Ni, Guiyan

AU - Gratten, Jacob

AU - Wray, Naomi R.

AU - Lee, Sang Hong

AU - Agerbo, Esben

AU - Demontis, Ditte

AU - Hansen, Thomas

AU - Hollegaard, Mads V.

AU - Hougaard, David M.

AU - Mattheisen, Manuel

AU - Mors, Ole

AU - Olsen, Line

AU - Rasmussen, Henrik B.

AU - Børglum, Anders D.

AU - Mortensen, Preben B.

AU - Werge, Thomas

AU - Pers, Tune Hannes

PY - 2018

Y1 - 2018

N2 - Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.

AB - Previous studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.

U2 - 10.1038/s41598-018-28160-z

DO - 10.1038/s41598-018-28160-z

M3 - Journal article

C2 - 29977057

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 10168

ER -

Age at first birth in women is genetically associated with increased risk of schizophrenia

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