Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies

Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perin...

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Veröffentlicht in:Molecular psychiatry Jg. 16; H. 12; S. 1203 - 1212
Hauptverfasser: Hultman, C M, Sandin, S, Levine, S Z, Lichtenstein, P, Reichenberg, A
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.12.2011
Nature Publishing Group
Schlagworte:
692/308/2779/174
692/699/476/1312
Adolescent
Adult
Age
Aging
Autism
Autistic Disorder - epidemiology
Autistic Disorder - genetics
Autistic Disorder - psychology
Behavioral Sciences
Biological and medical sciences
Biological Psychology
Child clinical studies
Cohort Studies
Databases, Factual - statistics & numerical data
Developmental disorders
Epidemiology
Epigenetics
Family Health - statistics & numerical data
Fathers
Female
Genetic aspects
Humans
Infantile autism
Male
Maternal Age
Medical sciences
Medicine
Medicine & Public Health
Meta-analysis
Middle Aged
Neurosciences
original-article
Parity
Paternal Age
Pharmacotherapy
Phenotypes
Population studies
Population-based studies
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Risk Factors
Siblings
Siblings - psychology
Sweden - epidemiology
Systematic review
Sweden
epidemiology
paternal age
perinatal
autism
Autism
Paternal age
Population-based survey
Risk factor
Perinatal
Developmental disorder
Review
Epidemiology
Public health
Metaanalysis
de-novo
Risk
meta analysis
ISSN:1359-4184, 1476-5578, 1476-5578
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Abstract Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort ( N =1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases ( N =883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ⩾50 years were 2.2 times (95% confidence interval: 1.26–3.88: P =0.006) more likely to have autism than offspring of men aged ⩽29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity ( P <0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
AbstractList Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1075588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ≥50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged ≤29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ≥50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged ≤29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ⩾50 years were 2.2 times (95% confidence interval: 1.26–3.88: P=0.006) more likely to have autism than offspring of men aged ⩽29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ≥50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged ≤29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ≥50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged ≤29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N =1 075588) was established. Linkage to the National Patient Register ascertained all autism cases (N = 883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged [??] 50 years were 2.2 times (95% confidence interval: 1.26-3.88: P =0.006) more likely to have autism than offspring of men aged [??] 29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P< 0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging. Molecular Psychiatry (2011) 16,1203-1212; doi: 10.1038/mp.2010.121; published online 30 November 2010 Keywords: autism; epidemiology; paternal age; perinatal
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N =1 075588) was established. Linkage to the National Patient Register ascertained all autism cases (N = 883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged [??] 50 years were 2.2 times (95% confidence interval: 1.26-3.88: P =0.006) more likely to have autism than offspring of men aged [??] 29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P< 0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort ( N =1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases ( N =883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged ⩾50 years were 2.2 times (95% confidence interval: 1.26–3.88: P =0.006) more likely to have autism than offspring of men aged ⩽29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity ( P <0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Advanced paternal age has been suggested as risk factors for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (I) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (II) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (III) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10 birth-years cohort (N=1,075,588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth-cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth-cohort autism risk increased monotonically with increasing paternal age. Offspring of men 50 years or older were 2.2 times (95% confidence interval: 1.26-3.88: p=0.006) more likely to have autism than offspring of men 29 years or younger, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (p<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de-novo aberration and mutations or epigenetic alterations associated with ageing.
Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between paternal age and autism in the offspring (1) persists controlling for documented autism risk factors, including family psychiatric history, perinatal conditions, infant characteristics and demographic variables; (2) may be explained by familial traits associated with the autism phenotype, or confounding by parity; and (3) is consistent across epidemiological studies. Multiple study methods were adopted. First, a Swedish 10-year birth cohort (N=1 075 588) was established. Linkage to the National Patient Register ascertained all autism cases (N=883). Second, 660 families identified within the birth cohort had siblings discordant for autism. Finally, meta-analysis included population-based epidemiological studies. In the birth cohort, autism risk increased monotonically with increasing paternal age. Offspring of men aged greater than or equal to 50 years were 2.2 times (95% confidence interval: 1.26-3.88: P=0.006) more likely to have autism than offspring of men aged less than or equal to 29 years, after controlling for maternal age and documented risk factors for autism. Within-family analysis of discordant siblings showed that affected siblings had older paternal age, adjusting for maternal age and parity (P<0.0001). Meta-analysis demonstrated advancing paternal age association with increased risk of autism across studies. These findings provide the strongest evidence to date that advanced paternal age is a risk factor for autism in the offspring. Possible biological mechanisms include de novo aberration and mutations or epigenetic alterations associated with aging.
Audience Academic
Author Hultman, C M
Sandin, S
Reichenberg, A
Lichtenstein, P
Levine, S Z
Author_xml – sequence: 1
  givenname: C M
  surname: Hultman
  fullname: Hultman, C M
  organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
– sequence: 2
  givenname: S
  surname: Sandin
  fullname: Sandin, S
  organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
– sequence: 3
  givenname: S Z
  surname: Levine
  fullname: Levine, S Z
  organization: Department of Criminology, Bar Ilan University
– sequence: 4
  givenname: P
  surname: Lichtenstein
  fullname: Lichtenstein, P
  organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
– sequence: 5
  givenname: A
  surname: Reichenberg
  fullname: Reichenberg, A
  email: avi.reichenberg@kcl.ac.uk, avi.reichenberg@mssm.edu
  organization: Department of Psychosis Studies, Institute of Psychiatry, King's Health Partners, King's College London, Department of Psychiatry, Mount Sinai School of Medicine
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Issue 12
Keywords epidemiology
paternal age
perinatal
autism
Autism
Paternal age
Population-based survey
Risk factor
Perinatal
Developmental disorder
Review
Epidemiology
Public health
Metaanalysis
de-novo
Risk
meta analysis
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PublicationTitle Molecular psychiatry
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Nature Publishing Group
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Snippet Advanced paternal age has been suggested as a risk factor for autism, but empirical evidence is mixed. This study examines whether the association between...
Advanced paternal age has been suggested as risk factors for autism, but empirical evidence is mixed. This study examines whether the association between...
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692/699/476/1312
Adolescent
Adult
Age
Aging
Autism
Autistic Disorder - epidemiology
Autistic Disorder - genetics
Autistic Disorder - psychology
Behavioral Sciences
Biological and medical sciences
Biological Psychology
Child clinical studies
Cohort Studies
Databases, Factual - statistics & numerical data
Developmental disorders
Epidemiology
Epigenetics
Family Health - statistics & numerical data
Fathers
Female
Genetic aspects
Humans
Infantile autism
Male
Maternal Age
Medical sciences
Medicine
Medicine & Public Health
Meta-analysis
Middle Aged
Neurosciences
original-article
Parity
Paternal Age
Pharmacotherapy
Phenotypes
Population studies
Population-based studies
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Risk Factors
Siblings
Siblings - psychology
Sweden - epidemiology
Systematic review
Title Advancing paternal age and risk of autism: new evidence from a population-based study and a meta-analysis of epidemiological studies
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