The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability / Sherlly XIE in Autism Research, 13-12 (December 2020)  

Public ISBD [article]  inAutism Research > 13-12 (December 2020) . - p.2242-2250 Titre : The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability Type de document : Texte imprimé et/ou numérique Auteurs : Sherlly XIE, Auteur ; Håkan KARLSSON, Auteur ; Christina DALMAN, Auteur ; Linnea WIDMAN, Auteur ; Dheeraj RAI, Auteur ; Renee M. GARDNER, Auteur ; Cecilia MAGNUSSON, Auteur ; Sven SANDIN, Auteur ; Loni P. TABB, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Brian K. LEE, Auteur Article en page(s) : p.2242-2250 Langues : Anglais (eng) Mots-clés : autism spectrum disorders  familial risk  family study  heritability  intellectual disability Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population-based cohort study, we examined the familial risk and heritability of ASD with and without co-occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD-ID) using register-based diagnosis data of 567,436 index persons born in 1984-2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD-ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD-ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2-18.6) and 7.4 (5.5-10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD-ID. The broad-sense heritability (95% CI) for ASD?-?ID and ASD+ID were 64.6% (46.0-100.0%) and 33.4% (14.4-58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. LAY SUMMARY: Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well-understood. In a population-based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. En ligne : http://dx.doi.org/10.1002/aur.2417 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=434 [article] The Familial Risk of Autism Spectrum Disorder with and without Intellectual Disability [Texte imprimé et/ou numérique] / Sherlly XIE, Auteur ; Håkan KARLSSON, Auteur ; Christina DALMAN, Auteur ; Linnea WIDMAN, Auteur ; Dheeraj RAI, Auteur ; Renee M. GARDNER, Auteur ; Cecilia MAGNUSSON, Auteur ; Sven SANDIN, Auteur ; Loni P. TABB, Auteur ; Craig J. NEWSCHAFFER, Auteur ; Brian K. LEE, Auteur . - p.2242-2250. Langues : Anglais (eng) in Autism Research > 13-12 (December 2020) . - p.2242-2250 Mots-clés : autism spectrum disorders  familial risk  family study  heritability  intellectual disability Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well understood. In this population-based cohort study, we examined the familial risk and heritability of ASD with and without co-occurring intellectual disability (ID). We estimated odds ratios and heritability of ASD with ID (ASD+ID) and ASD without ID (ASD-ID) using register-based diagnosis data of 567,436 index persons born in 1984-2009 in Stockholm County, Sweden, and their parents, siblings, cousins, aunts, and uncles. The familial risk profile exhibited differences between ASD-ID and ASD+ID, most notably for index persons with affected parents. For example, for an index person who had at least one parent with ASD, the child's odds of ASD-ID and ASD+ID (95% confidence interval (CI)) increased by 16.2 (14.2-18.6) and 7.4 (5.5-10.0) folds, respectively. The more closely related a family member with ASD was, the greater the observed risk was of ASD in the index person, especially for ASD-ID. The broad-sense heritability (95% CI) for ASD?-?ID and ASD+ID were 64.6% (46.0-100.0%) and 33.4% (14.4-58.4%), respectively. Familial risk and heritability of ASD may vary by intellectual ability, which implies that risk factors between these ASD phenotypes may differ. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. LAY SUMMARY: Autism spectrum disorder (ASD) is highly heritable, yet how its familial risk and heritability may vary by cognitive ability is not well-understood. In a population-based cohort study on families of 567,436 index persons using Swedish registers data, we found that the familial risk profile differed between ASD with and without intellectual disability. Our findings from the heritability analysis and familial risk analysis suggest that ASD-ID may have a greater genetic basis than ASD+ID, although this should be verified in future studies. En ligne : http://dx.doi.org/10.1002/aur.2417 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=434

Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study / B. Y. PARK in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 3p. Titre : Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Type de document : Texte imprimé et/ou numérique Auteurs : B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study [Texte imprimé et/ou numérique] / B. Y. PARK, Auteur ; Brian K. LEE, Auteur ; Igor BURSTYN, Auteur ; Loni P. TABB, Auteur ; J. A. KEELAN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; O. MONTGOMERY, Auteur ; C. J. NEWSCHAFFER, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 3p. Mots-clés : Adult  Androstenedione/*metabolism  Autism Spectrum Disorder/metabolism/*psychology  Chromatography, Liquid  Cohort Studies  Dehydroepiandrosterone/*metabolism  Female  Fetal Blood/*metabolism  Humans  Infant  Linear Models  Longitudinal Studies  Male  Pregnancy  Prospective Studies  Risk Assessment  Severity of Illness Index  Siblings/*psychology  Tandem Mass Spectrometry  Testosterone/*metabolism  *Autism  *Sex difference  *Sibling  *Testosterone  *Umbilical cord blood Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) affects more than 1% of children in the USA. The male-to-female prevalence ratio of roughly 4:1 in ASD is a well-recognized but poorly understood phenomenon. An explicit focus on potential etiologic pathways consistent with this sex difference, such as those involving prenatal androgen exposure, may help elucidate causes of ASD. Furthermore, the multi-threshold liability model suggests that the genetic mechanisms in females with ASD may be distinct and may modulate ASD risk in families with female ASD in the pedigree. METHODS: We examined umbilical cord blood from 137 children in the Early Autism Risk Longitudinal Investigation (EARLI) cohort. EARLI is an ASD-enriched risk cohort with all children having an older sibling already diagnosed with ASD. Fetal testosterone (T), androstenedione (A4), and dehyroepiandrosterone (DHEA) levels were measured in cord blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Robust linear regression models were used to determine associations between cord blood androgen levels and 12-month Autism Observation Scales for Infants (AOSI) scores and 36-month Social Responsiveness Scale (SRS) scores adjusting for potential confounders. RESULTS: Increasing androgens were not associated with increasing 12-month AOSI score or 36-month total SRS score in either boys or girls. However, the association between T and autistic traits among subjects with a female older affected sibling was greater at 12 months (test of interaction, P = 0.008) and deficits in reciprocal social behavior at 36 months were also greater (test of interaction, P = 0.006) than in subjects whose older affected sibling was male. CONCLUSIONS: While increased prenatal testosterone levels were not associated with autistic traits at 12 or 36 months, our findings of a positive association in infants whose older ASD-affected siblings were female suggests an androgen-related mechanism that may be dependent on, or related to, genetic liability factors present more often in families containing female ASD cases. However, this initial finding, based on a small subgroup of our sample, should be interpreted with considerable caution. En ligne : http://dx.doi.org/10.1186/s13229-017-0118-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

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