Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.
Détails
Etat: Public
Version: Final published version
ID Serval
serval:BIB_FA7E8A43283E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities.
Périodique
Jama Psychiatry
Collaborateur⸱rice⸱s
Cardiff University Experiences of Children With Copy Number Variants (ECHO) Study, 16p11.2 European Consortium, Simons Variation in Individuals Project (VIP) Consortium
Contributeur⸱rice⸱s
Knoers VA., Martinet D., Belfiore M., Cuvellier JC., de Vries B., Delrue MA., Doco-Fenzy M., Lebel R., Leheup B., Lewis S., Mencarelli MA., Minet JC., Vincent-Delorme C., Moerman A., Mucciolo M., Ounap K., Rajcan-Separovic E., Renieri A., Sanlaville D., Faas BH., Koolen DA., Vulto-van Silfhout A., de Leeuw N., Rosenfeld JA., Filges I., Achatz E., Roetzer KM., Bonneau D., Guichet A., Lazaro L., Plessis G., Kroisel PM., Reis A., Jonveaux P., Chantot-Bastaraud S., Rauch A., Demeer B., Nordgren A., Labalme A., Ferrarini A., Ramelli GP., Guilmatre A., Joly-Helas G., Haize S., Layet V., Le Gallic S., de Fréminville B., Touraine R., Van Binsbergen E., Mathieu-Dramard M., Barth M., Blaumeiser B., Masurel A., Cailler P., Olivier-Faivre L., Malacarne M., Coutton C., Dieterich K., Satre V., Wallgren-Pettersson C., Tensgrom C., Kaksonen S., Duban-Bedu B., Holder M., Rossi M., Gaillard D., Bock D., Bednarek N., Guillin O., Bizzarri V., Flori E., Silengo M., Kooy RF., Aboura A., Beri M., Delobel B., Drunat S., Jaros Z., Kolk A., Reigo A., Zufferey F., Beckmann N., Faravelli F., Alupay H., Aaronson B., Ackerman S., Ankenman K., Anwar A., Atwell C., Bowe A., Beaudet AL., Benedetti M., Berg J., Berman J., Berry LN., Bibb AL., Blaskey L., Brennan J., Brewton CM., Buckner R., Bukshpun P., Burko J., Cali P., Cerban B., Chang Y., Cheong M., Chow V., Chu Z., Chudnovskaya D., Cornew L., Dale C., Dell J., Dempsey AG., Deschamps T., Earl R., Edgar J., Elgin J., Olson JE., Evans YL., Findlay A., Fischbach GD., Fisk C., Fregeau B., Gaetz B., Gaetz L., Garza S., Gerdts J., Glenn O., Gobuty SE., Golembski R., Greenup M., Heiken K., Hines K., Hinkley L., Jackson FI., Jenkins J.<Suffix>3rd</Suffix> , Jeremy RJ., Johnson K., Kanne SM., Kessler S., Khan SY., Ku M., Kuschner E., Laakman AL., Lam P., Lasala MW., Lee H., LaGuerre K., Levy S., Lian Cavanagh A., Llorens AV., Loftus Campe K., Luks TL., Marco EJ., Martin S., Martin AJ., Marzano G., Masson C., McGovern KE., McNally Keehn R., Miller DT., Miller FK., Moss TJ., Murray R., Nagarajan SS., Nowell KP., Owen J., Paal AM., Packer A., Page PZ., Paul BM., Peters A., Peterson D., Poduri A., Pojman NJ., Porche K., Proud MB., Qasmieh S., Ramocki MB., Reilly B., Roberts TP., Shaw D., Sinha T., Smith-Packard B., Snow Gallagher A., Swarnakar V., Thieu T., Triantafallou C., Vaughan R., Wakahiro M., Wallace A., Ward T., Wenegrat J., Wolken A.
ISSN
2168-6238 (Electronic)
ISSN-L
2168-622X
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
73
Numéro
1
Pages
20-30
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
IMPORTANCE: The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI).
OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD.
DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives.
MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data.
RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies.
CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
OBJECTIVES: To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD.
DESIGN, SETTING, AND PARTICIPANTS: This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives.
MAIN OUTCOMES AND MEASURES: Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data.
RESULTS: Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P < .001). However, broad variation in FSIQ was found, with a 19.4- and 2.0-fold increase in the proportion of FSIQ scores that were very low (≤40) and higher than the mean (>100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies.
CONCLUSIONS AND RELEVANCE: The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits.
Mots-clé
Adolescent, Adult, Autism Spectrum Disorder/epidemiology, Autism Spectrum Disorder/genetics, Autistic Disorder/epidemiology, Autistic Disorder/genetics, Case-Control Studies, Cerebellum/abnormalities, Child, Child, Preschool, Chromosome Deletion, Chromosome Disorders/epidemiology, Chromosome Disorders/genetics, Chromosome Duplication, Chromosomes, Human, Pair 16/genetics, Cognition, Cohort Studies, Comorbidity, DNA Copy Number Variations, Developmental Disabilities/epidemiology, Developmental Disabilities/genetics, Epilepsy/epidemiology, Epilepsy/genetics, Female, Humans, Intellectual Disability/epidemiology, Intellectual Disability/genetics, Male, Microcephaly/epidemiology, Microcephaly/genetics, Middle Aged, Nervous System Malformations/epidemiology, Nervous System Malformations/genetics, Schizophrenia/epidemiology, Schizophrenia/genetics, Schizophrenic Psychology, Young Adult
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/01/2016 16:55
Dernière modification de la notice
20/08/2019 16:25
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