Aarhus Universitet

Tine Brink Henriksen

Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia

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Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia. / Debost, Jean-Christophe; Petersen, Liselotte; Grove, Jakob; Khashan, Ali; Henriksen, Tine; Mors, Ole; Hollegaard, Mads; Hougaard, David; Nyegaard, Mette; Børglum, Anders; Mortensen, Preben Bo.

I: Psychoneuroendocrinology, Bind 60, 11.06.2015, s. 18-27.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{03e07eca0a654890b7ff530f69b8b815,
title = "Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia",
abstract = "BACKGROUND: To examine the risk of schizophrenia in a Danish population after exposure to early life stress, and whether this risk is modified by DNA sequence variation, specifically two single nucleotide polymorphisms (SNPs) (rs5479 and rs56303414) from the gene HSD11B2. This gene encodes the enzyme 11-β hydroxysteroid dehydrogenase type 2 which converts active cortisol into inactive cortisone.METHODS: A two-stage analysis involving (1) a population-based cohort study, and (2) a nested case-control study using genotype information. Stage 1 included 1,141,447 people; here, we calculated incidence rate ratios (IRR) for the risk of schizophrenia among children of mothers who experienced loss or serious illness of close relatives before, during, and after pregnancy. In stage 2, we genotyped rs5479 and rs56303414 among 1275 schizophrenia cases and 1367 controls, and investigated interactions between genotypes and early life stress on the risk of schizophrenia.RESULTS: In stage 1, no increased risk of schizophrenia was found in offspring after exposure during pregnancy, but offspring exposed to early life stress at age 0-2 years had a significantly increased risk of schizophrenia (adjusted IRR 1.18, 95{\%} confidence interval 1.07-1.31). For rs5479, the minor allele was nucleotide A, and the major allele was nucleotide C. No interaction was found between rs5479 and exposure during pregnancy. Individuals with the minor A allele of rs5479, however, had a significantly increased risk of schizophrenia after exposure to early life stress at age 3-9 years (adjusted IRR 2.06, 1.04-4.06). No interaction was found between rs56303414 and exposure in any of the time periods.CONCLUSION: No association was found between exposure to early life stress during pregnancy and schizophrenia in the offspring investigated, whereas individuals exposed to early life stress within the first two years of life had an increased risk. No interaction was found between HSD11B2 and exposure during pregnancy, but individuals with the A allele of rs5479 had an increased risk of schizophrenia after exposure at age 3-9 years.",
author = "Jean-Christophe Debost and Liselotte Petersen and Jakob Grove and Ali Khashan and Tine Henriksen and Ole Mors and Mads Hollegaard and David Hougaard and Mette Nyegaard and Anders B{\o}rglum and Mortensen, {Preben Bo}",
note = "Copyright {\circledC} 2015 Elsevier Ltd. All rights reserved.",
year = "2015",
month = "6",
day = "11",
doi = "10.1016/j.psyneuen.2015.05.013",
language = "English",
volume = "60",
pages = "18--27",
journal = "Psychoneuroendocrinology",
issn = "0306-4530",
publisher = "Pergamon Press",

}

RIS

TY - JOUR

T1 - Investigating interactions between early life stress and two single nucleotide polymorphisms in HSD11B2 on the risk of schizophrenia

AU - Debost, Jean-Christophe

AU - Petersen, Liselotte

AU - Grove, Jakob

AU - Khashan, Ali

AU - Henriksen, Tine

AU - Mors, Ole

AU - Hollegaard, Mads

AU - Hougaard, David

AU - Nyegaard, Mette

AU - Børglum, Anders

AU - Mortensen, Preben Bo

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/6/11

Y1 - 2015/6/11

N2 - BACKGROUND: To examine the risk of schizophrenia in a Danish population after exposure to early life stress, and whether this risk is modified by DNA sequence variation, specifically two single nucleotide polymorphisms (SNPs) (rs5479 and rs56303414) from the gene HSD11B2. This gene encodes the enzyme 11-β hydroxysteroid dehydrogenase type 2 which converts active cortisol into inactive cortisone.METHODS: A two-stage analysis involving (1) a population-based cohort study, and (2) a nested case-control study using genotype information. Stage 1 included 1,141,447 people; here, we calculated incidence rate ratios (IRR) for the risk of schizophrenia among children of mothers who experienced loss or serious illness of close relatives before, during, and after pregnancy. In stage 2, we genotyped rs5479 and rs56303414 among 1275 schizophrenia cases and 1367 controls, and investigated interactions between genotypes and early life stress on the risk of schizophrenia.RESULTS: In stage 1, no increased risk of schizophrenia was found in offspring after exposure during pregnancy, but offspring exposed to early life stress at age 0-2 years had a significantly increased risk of schizophrenia (adjusted IRR 1.18, 95% confidence interval 1.07-1.31). For rs5479, the minor allele was nucleotide A, and the major allele was nucleotide C. No interaction was found between rs5479 and exposure during pregnancy. Individuals with the minor A allele of rs5479, however, had a significantly increased risk of schizophrenia after exposure to early life stress at age 3-9 years (adjusted IRR 2.06, 1.04-4.06). No interaction was found between rs56303414 and exposure in any of the time periods.CONCLUSION: No association was found between exposure to early life stress during pregnancy and schizophrenia in the offspring investigated, whereas individuals exposed to early life stress within the first two years of life had an increased risk. No interaction was found between HSD11B2 and exposure during pregnancy, but individuals with the A allele of rs5479 had an increased risk of schizophrenia after exposure at age 3-9 years.

AB - BACKGROUND: To examine the risk of schizophrenia in a Danish population after exposure to early life stress, and whether this risk is modified by DNA sequence variation, specifically two single nucleotide polymorphisms (SNPs) (rs5479 and rs56303414) from the gene HSD11B2. This gene encodes the enzyme 11-β hydroxysteroid dehydrogenase type 2 which converts active cortisol into inactive cortisone.METHODS: A two-stage analysis involving (1) a population-based cohort study, and (2) a nested case-control study using genotype information. Stage 1 included 1,141,447 people; here, we calculated incidence rate ratios (IRR) for the risk of schizophrenia among children of mothers who experienced loss or serious illness of close relatives before, during, and after pregnancy. In stage 2, we genotyped rs5479 and rs56303414 among 1275 schizophrenia cases and 1367 controls, and investigated interactions between genotypes and early life stress on the risk of schizophrenia.RESULTS: In stage 1, no increased risk of schizophrenia was found in offspring after exposure during pregnancy, but offspring exposed to early life stress at age 0-2 years had a significantly increased risk of schizophrenia (adjusted IRR 1.18, 95% confidence interval 1.07-1.31). For rs5479, the minor allele was nucleotide A, and the major allele was nucleotide C. No interaction was found between rs5479 and exposure during pregnancy. Individuals with the minor A allele of rs5479, however, had a significantly increased risk of schizophrenia after exposure to early life stress at age 3-9 years (adjusted IRR 2.06, 1.04-4.06). No interaction was found between rs56303414 and exposure in any of the time periods.CONCLUSION: No association was found between exposure to early life stress during pregnancy and schizophrenia in the offspring investigated, whereas individuals exposed to early life stress within the first two years of life had an increased risk. No interaction was found between HSD11B2 and exposure during pregnancy, but individuals with the A allele of rs5479 had an increased risk of schizophrenia after exposure at age 3-9 years.

U2 - 10.1016/j.psyneuen.2015.05.013

DO - 10.1016/j.psyneuen.2015.05.013

M3 - Journal article

VL - 60

SP - 18

EP - 27

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

SN - 0306-4530

ER -