Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.

The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity.

Pizzagalli F;BRUSCO, Alfredo;GIACHINO, Daniela Francesca;MANDRILE, Giorgia;
2015

Abstract

Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.
20
1
140
147
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320286/
http://www.nature.com/mp/journal/v20/n1/pdf/mp2014145a.pdf
Adolescent; Adult; Anthropometry; Arabidopsis Proteins; Autistic Disorder; Body Mass Index; Brain; Brain Mapping; Child; Chromosomes, Human, Pair 16; DNA Copy Number Variations; Female; Gene Dosage; Genetic Association Studies; Humans; Intramolecular Transferases; Male; Middle Aged; Obesity; Phenotype; Psychiatric Status Rating Scales; Schizophrenia; Young Adult
Maillard AM;Ruef A;Pizzagalli F;Migliavacca E;Hippolyte L;Adaszewski S;Dukart J;Ferrari C;Conus P;Männik K;Zazhytska M;Siffredi V;Maeder P;Kutalik Z;Kherif F;Hadjikhani N;Beckmann JS;Reymond A;Draganski B;Jacquemont S;16p11.2 European Consortium including Addor MC; Andrieux J; Arveiler B; Baujat G; Béna F; Bouquillon S; Boute O; Brusco A; Campion D; David A; Delrue MA; Doco-Fenzy M; Fagerberg C; Faivre L; Forzano F; Giachino D; Guichet A; Guillin O; Héron D; Isidor B; Jacquette A; Journel H; Keren B; Lacombe D; Le Caignec C; Lespinasse J; Mandrile G; Mathieu-Dramard M; Mignot C; Petit F; Plessis G; Prieur F; Sanlaville D; Van Haelst M; Van Maldergem L
File in questo prodotto:
File Dimensione Formato  
2015_Maillard_brain structures_def.pdf

Accesso aperto

Descrizione: articolo
Tipo di file: PDF EDITORIALE
Dimensione 763.07 kB
Formato Adobe PDF
763.07 kB Adobe PDF Visualizza/Apri
2015_Maillard_brain structures_suppl.pdf

Accesso aperto

Descrizione: supplements
Tipo di file: MATERIALE NON BIBLIOGRAFICO
Dimensione 2.28 MB
Formato Adobe PDF
2.28 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/152956
Citazioni
  • ???jsp.display-item.citation.pmc??? 68
  • Scopus 110
  • ???jsp.display-item.citation.isi??? 109
social impact