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Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples / Kit K. ELAM in Development and Psychopathology, 36-1 (February 2024)
[article]
Titre : Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples Type de document : Texte imprimé et/ou numérique Auteurs : Kit K. ELAM, Auteur ; Kaitlin E. BOUNTRESS, Auteur ; Thao HA, Auteur ; Daniel S. SHAW, Auteur ; Melvin N. WILSON, Auteur ; Fazil ALIEV, Auteur ; Danielle M. DICK, Auteur ; Kathryn LEMERY-CHALFANT, Auteur Article en page(s) : p.82-91 Langues : Anglais (eng) Mots-clés : adolescence alcohol use externalizing longitudinal polygenic Index. décimale : PER Périodiques Résumé : Externalizing behavior in early adolescence is associated with alcohol use in adolescence and early adulthood and these behaviors often emerge as part of a developmental sequence. This pattern can be the result of heterotypic continuity, in which different behaviors emerge over time based on an underlying shared etiology. In particular, there is largely a shared genetic etiology underlying externalizing and substance use behaviors. We examined whether polygenic risk for alcohol use disorder predicted (1) externalizing behavior in early adolescence and alcohol use in adolescence in the Early Steps Multisite sample and (2) externalizing behavior in adolescence and alcohol use in early adulthood in the Project Alliance 1 (PAL1) sample. We examined associations separately for African Americans and European Americans. When examining European Americans in the Early Steps sample, greater polygenic risk was associated with externalizing behavior in early adolescence. In European Americans in PAL1, we found greater polygenic risk was associated with alcohol use in early adulthood. Effects were largely absent in African Americans in both samples. Results imply that genetic predisposition for alcohol use disorder may increase risk for externalizing and alcohol use as these behaviors emerge developmentally. En ligne : https://dx.doi.org/10.1017/S0954579422000980 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=523
in Development and Psychopathology > 36-1 (February 2024) . - p.82-91[article] Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples [Texte imprimé et/ou numérique] / Kit K. ELAM, Auteur ; Kaitlin E. BOUNTRESS, Auteur ; Thao HA, Auteur ; Daniel S. SHAW, Auteur ; Melvin N. WILSON, Auteur ; Fazil ALIEV, Auteur ; Danielle M. DICK, Auteur ; Kathryn LEMERY-CHALFANT, Auteur . - p.82-91.
Langues : Anglais (eng)
in Development and Psychopathology > 36-1 (February 2024) . - p.82-91
Mots-clés : adolescence alcohol use externalizing longitudinal polygenic Index. décimale : PER Périodiques Résumé : Externalizing behavior in early adolescence is associated with alcohol use in adolescence and early adulthood and these behaviors often emerge as part of a developmental sequence. This pattern can be the result of heterotypic continuity, in which different behaviors emerge over time based on an underlying shared etiology. In particular, there is largely a shared genetic etiology underlying externalizing and substance use behaviors. We examined whether polygenic risk for alcohol use disorder predicted (1) externalizing behavior in early adolescence and alcohol use in adolescence in the Early Steps Multisite sample and (2) externalizing behavior in adolescence and alcohol use in early adulthood in the Project Alliance 1 (PAL1) sample. We examined associations separately for African Americans and European Americans. When examining European Americans in the Early Steps sample, greater polygenic risk was associated with externalizing behavior in early adolescence. In European Americans in PAL1, we found greater polygenic risk was associated with alcohol use in early adulthood. Effects were largely absent in African Americans in both samples. Results imply that genetic predisposition for alcohol use disorder may increase risk for externalizing and alcohol use as these behaviors emerge developmentally. En ligne : https://dx.doi.org/10.1017/S0954579422000980 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=523 Differential susceptibility 2.0: Are the same children affected by different experiences and exposures? / Jay BELSKY in Development and Psychopathology, 34-3 (August 2022)
[article]
Titre : Differential susceptibility 2.0: Are the same children affected by different experiences and exposures? Type de document : Texte imprimé et/ou numérique Auteurs : Jay BELSKY, Auteur ; Xiaoya ZHANG, Auteur ; Kristina SAYLER, Auteur Article en page(s) : p.1025-1033 Langues : Anglais (eng) Mots-clés : differential susceptibility childcare domain specific domain general polygenic Index. décimale : PER Périodiques Résumé : Differential susceptibility theory stipulates that some children are more susceptible than others to both supportive and adverse developmental experiences/exposures. What remains unclear is whether the same individuals are most affected by different exposures (i.e., domain general vs. specific). We address this issue empirically for the first time using, for illustrative and proof-of-principle purposes, a novel influence-statistics’ method with data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. Results indicated that previously documented effects of greater quality of care on enhanced pre-academic skills and greater quantity of care on more behavior problems apply mostly to different children. Analyses validating the new method indicated, as predicted, that (a) the quantity-of-care effect applied principally to children from more socioeconomically advantaged families and that (b) being highly susceptible to both, one or neither childcare effect varied as a function of a three-gene, polygenic-plasticity score (serotonin transporter linked polymorphic region [5-HTTLPR], dopamine receptor D4 [DRD4], brain-derived neurotrophic factor [BDNF]) in a dose “response manner (i.e., 2>1>0). While domain-specific findings involving child-care effects cannot be generalized to other environmental influences, the influence-statistics’ approach appears well suited for investigating the generality “specificity of environment effects, that is, of œdifferential, differential susceptibility. En ligne : http://dx.doi.org/10.1017/S0954579420002205 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=485
in Development and Psychopathology > 34-3 (August 2022) . - p.1025-1033[article] Differential susceptibility 2.0: Are the same children affected by different experiences and exposures? [Texte imprimé et/ou numérique] / Jay BELSKY, Auteur ; Xiaoya ZHANG, Auteur ; Kristina SAYLER, Auteur . - p.1025-1033.
Langues : Anglais (eng)
in Development and Psychopathology > 34-3 (August 2022) . - p.1025-1033
Mots-clés : differential susceptibility childcare domain specific domain general polygenic Index. décimale : PER Périodiques Résumé : Differential susceptibility theory stipulates that some children are more susceptible than others to both supportive and adverse developmental experiences/exposures. What remains unclear is whether the same individuals are most affected by different exposures (i.e., domain general vs. specific). We address this issue empirically for the first time using, for illustrative and proof-of-principle purposes, a novel influence-statistics’ method with data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care. Results indicated that previously documented effects of greater quality of care on enhanced pre-academic skills and greater quantity of care on more behavior problems apply mostly to different children. Analyses validating the new method indicated, as predicted, that (a) the quantity-of-care effect applied principally to children from more socioeconomically advantaged families and that (b) being highly susceptible to both, one or neither childcare effect varied as a function of a three-gene, polygenic-plasticity score (serotonin transporter linked polymorphic region [5-HTTLPR], dopamine receptor D4 [DRD4], brain-derived neurotrophic factor [BDNF]) in a dose “response manner (i.e., 2>1>0). While domain-specific findings involving child-care effects cannot be generalized to other environmental influences, the influence-statistics’ approach appears well suited for investigating the generality “specificity of environment effects, that is, of œdifferential, differential susceptibility. En ligne : http://dx.doi.org/10.1017/S0954579420002205 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=485 Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms / Evelien VAN ASSCHE in Journal of Child Psychology and Psychiatry, 58-12 (December 2017)
[article]
Titre : Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms Type de document : Texte imprimé et/ou numérique Auteurs : Evelien VAN ASSCHE, Auteur ; Tim MOONS, Auteur ; Ozan CINAR, Auteur ; Wolfgang VIECHTBAUER, Auteur ; Albertine J. OLDEHINKEL, Auteur ; Karla VAN LEEUWEN, Auteur ; Karine VERSCHUEREN, Auteur ; Hilde COLPIN, Auteur ; Diether LAMBRECHTS, Auteur ; Wim VAN DEN NOORTGATE, Auteur ; Luc GOOSSENS, Auteur ; Stephan CLAES, Auteur ; Ruud VAN WINKEL, Auteur Article en page(s) : p.1301-1309 Langues : Anglais (eng) Mots-clés : Gene–environment interaction polygenic parenting gene-based testing adolescents depression Index. décimale : PER Périodiques Résumé : Background Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. Methods Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p < 1.90 × 10?4 were examined in an independent replication sample of Dutch adolescents (N = 1354). Results Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10?5) and GABRR2 (p = 9.05 × 10?6). No genes interacted significantly with psychological control or harsh punishment. Gene-based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene-based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10?4). Conclusions We present a gene-based method for gene–environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E. En ligne : http://dx.doi.org/10.1111/jcpp.12766 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=326
in Journal of Child Psychology and Psychiatry > 58-12 (December 2017) . - p.1301-1309[article] Gene-based interaction analysis shows GABAergic genes interacting with parenting in adolescent depressive symptoms [Texte imprimé et/ou numérique] / Evelien VAN ASSCHE, Auteur ; Tim MOONS, Auteur ; Ozan CINAR, Auteur ; Wolfgang VIECHTBAUER, Auteur ; Albertine J. OLDEHINKEL, Auteur ; Karla VAN LEEUWEN, Auteur ; Karine VERSCHUEREN, Auteur ; Hilde COLPIN, Auteur ; Diether LAMBRECHTS, Auteur ; Wim VAN DEN NOORTGATE, Auteur ; Luc GOOSSENS, Auteur ; Stephan CLAES, Auteur ; Ruud VAN WINKEL, Auteur . - p.1301-1309.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 58-12 (December 2017) . - p.1301-1309
Mots-clés : Gene–environment interaction polygenic parenting gene-based testing adolescents depression Index. décimale : PER Périodiques Résumé : Background Most gene-environment interaction studies (G × E) have focused on single candidate genes. This approach is criticized for its expectations of large effect sizes and occurrence of spurious results. We describe an approach that accounts for the polygenic nature of most psychiatric phenotypes and reduces the risk of false-positive findings. We apply this method focusing on the role of perceived parental support, psychological control, and harsh punishment in depressive symptoms in adolescence. Methods Analyses were conducted on 982 adolescents of Caucasian origin (Mage (SD) = 13.78 (.94) years) genotyped for 4,947 SNPs in 263 genes, selected based on a literature survey. The Leuven Adolescent Perceived Parenting Scale (LAPPS) and the Parental Behavior Scale (PBS) were used to assess perceived parental psychological control, harsh punishment, and support. The Center for Epidemiologic Studies Depression Scale (CES-D) was the outcome. We used gene-based testing taking into account linkage disequilibrium to identify genes containing SNPs exhibiting an interaction with environmental factors yielding a p-value per single gene. Significant results at the corrected p-value of p < 1.90 × 10?4 were examined in an independent replication sample of Dutch adolescents (N = 1354). Results Two genes showed evidence for interaction with perceived support: GABRR1 (p = 4.62 × 10?5) and GABRR2 (p = 9.05 × 10?6). No genes interacted significantly with psychological control or harsh punishment. Gene-based analysis was unable to confirm the interaction of GABRR1 or GABRR2 with support in the replication sample. However, for GABRR2, but not GABRR1, the correlation of the estimates between the two datasets was significant (r (46) = .32; p = .027) and a gene-based analysis of the combined datasets supported GABRR2 × support interaction (p = 1.63 × 10?4). Conclusions We present a gene-based method for gene–environment interactions in a polygenic context and show that genes interact differently with particular aspects of parenting. This accentuates the importance of polygenic approaches and the need to accurately assess environmental exposure in G × E. En ligne : http://dx.doi.org/10.1111/jcpp.12766 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=326 Suicidal ideation during adolescence: The roles of aggregate genetic liability for suicide attempts and negative life events in the past year / Séverine LANNOY in Journal of Child Psychology and Psychiatry, 63-10 (October 2022)
[article]
Titre : Suicidal ideation during adolescence: The roles of aggregate genetic liability for suicide attempts and negative life events in the past year Type de document : Texte imprimé et/ou numérique Auteurs : Séverine LANNOY, Auteur ; Becky MARS, Auteur ; Jon HERON, Auteur ; Alexis C. EDWARDS, Auteur Année de publication : 2022 Article en page(s) : p.1164-1173 Langues : Anglais (eng) Mots-clés : Adolescent Bullying Female Humans Male Risk Factors Schools Substance-Related Disorders Suicidal Ideation Suicide, Attempted Alspac environment genes polygenic suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicidal thoughts and behaviors (STB) constitute a central public health concern in adolescence. Previous studies emphasized the difficulty to cope with negative life events during adolescence as a risk factor for STB. Familial and genetic liability has also been documented to explain STB risk. Nevertheless, less is known about aggregate genetic liability and its possible interaction with negative life events. Moreover, information is needed to understand how these factors differently affect STB in boys and girls. METHODS: We evaluated suicidal ideation at 17years old and examined the role of aggregate genetic liability, negative life events, and their interaction in a sample of 2,571 adolescents. Aggregate genetic liability was measured using a polygenic score (PGS) for suicide attempts. Negative life events were assessed in the past year and included parental divorce and hospitalizations, death of friends and relatives, bullying, failure-related events, and involvement with drugs. We conducted univariable and multivariable general linear models stratified by sex and evaluated the interactions between PGS and negative life events in subsequent models. RESULTS: Analyses showed that suicidal ideation in boys is associated with failure to achieve something important (estimate=0.198), bullying (estimate=0.285), drug use (estimate=0.325), and parental death (estimate=0.923). In girls, both aggregate genetic liability (estimate=0.041) and negative life events (failure at school [estimate=0.120], failure to achieve something important [estimate=0.279], drug use [estimate=0.395], and bullying [estimate=0.472]) were associated with suicidal ideation. Interaction analyses suggested that PGS interacted with drug use and failures at school, though this would need additional support. CONCLUSIONS: These findings represent significant contributions to the fundamental understanding of STB in adolescence, suggesting to monitor the impact of negative life events during adolescence to better prevent suicide risk. Genetic liability is also of importance in girls and might influence the way they respond to environmental threats. En ligne : http://dx.doi.org/10.1111/jcpp.13653 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1164-1173[article] Suicidal ideation during adolescence: The roles of aggregate genetic liability for suicide attempts and negative life events in the past year [Texte imprimé et/ou numérique] / Séverine LANNOY, Auteur ; Becky MARS, Auteur ; Jon HERON, Auteur ; Alexis C. EDWARDS, Auteur . - 2022 . - p.1164-1173.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 63-10 (October 2022) . - p.1164-1173
Mots-clés : Adolescent Bullying Female Humans Male Risk Factors Schools Substance-Related Disorders Suicidal Ideation Suicide, Attempted Alspac environment genes polygenic suicidality Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicidal thoughts and behaviors (STB) constitute a central public health concern in adolescence. Previous studies emphasized the difficulty to cope with negative life events during adolescence as a risk factor for STB. Familial and genetic liability has also been documented to explain STB risk. Nevertheless, less is known about aggregate genetic liability and its possible interaction with negative life events. Moreover, information is needed to understand how these factors differently affect STB in boys and girls. METHODS: We evaluated suicidal ideation at 17years old and examined the role of aggregate genetic liability, negative life events, and their interaction in a sample of 2,571 adolescents. Aggregate genetic liability was measured using a polygenic score (PGS) for suicide attempts. Negative life events were assessed in the past year and included parental divorce and hospitalizations, death of friends and relatives, bullying, failure-related events, and involvement with drugs. We conducted univariable and multivariable general linear models stratified by sex and evaluated the interactions between PGS and negative life events in subsequent models. RESULTS: Analyses showed that suicidal ideation in boys is associated with failure to achieve something important (estimate=0.198), bullying (estimate=0.285), drug use (estimate=0.325), and parental death (estimate=0.923). In girls, both aggregate genetic liability (estimate=0.041) and negative life events (failure at school [estimate=0.120], failure to achieve something important [estimate=0.279], drug use [estimate=0.395], and bullying [estimate=0.472]) were associated with suicidal ideation. Interaction analyses suggested that PGS interacted with drug use and failures at school, though this would need additional support. CONCLUSIONS: These findings represent significant contributions to the fundamental understanding of STB in adolescence, suggesting to monitor the impact of negative life events during adolescence to better prevent suicide risk. Genetic liability is also of importance in girls and might influence the way they respond to environmental threats. En ligne : http://dx.doi.org/10.1111/jcpp.13653 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=486 In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? / Z. MOTAHARI in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)
[article]
Titre : In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? Type de document : Texte imprimé et/ou numérique Auteurs : Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur Article en page(s) : 7 p. Langues : Anglais (eng) Mots-clés : 22q11DS Cardiovascular Cognition Copy number variants Craniofacial Neural development Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p.[article] In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects? [Texte imprimé et/ou numérique] / Z. MOTAHARI, Auteur ; S. A. MOODY, Auteur ; T. M. MAYNARD, Auteur ; A. S. LAMANTIA, Auteur . - 7 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 7 p.
Mots-clés : 22q11DS Cardiovascular Cognition Copy number variants Craniofacial Neural development Polygenic Index. décimale : PER Périodiques Résumé : BACKGROUND: 22q11.2 deletion syndrome (22q11DS), a copy number variation (CNV) disorder, occurs in approximately 1:4000 live births due to a heterozygous microdeletion at position 11.2 (proximal) on the q arm of human chromosome 22 (hChr22) (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011). This disorder was known as DiGeorge syndrome, Velo-cardio-facial syndrome (VCFS) or conotruncal anomaly face syndrome (CTAF) based upon diagnostic cardiovascular, pharyngeal, and craniofacial anomalies (McDonald-McGinn and Sullivan, Medicine 90:1-18, 2011; Burn et al., J Med Genet 30:822-4, 1993) before this phenotypic spectrum was associated with 22q11.2 CNVs. Subsequently, 22q11.2 deletion emerged as a major genomic lesion associated with vulnerability for several clinically defined behavioral deficits common to a number of neurodevelopmental disorders (Fernandez et al., Principles of Developmental Genetics, 2015; Robin and Shprintzen, J Pediatr 147:90-6, 2005; Schneider et al., Am J Psychiatry 171:627-39, 2014). RESULTS: The mechanistic relationships between heterozygously deleted 22q11.2 genes and 22q11DS phenotypes are still unknown. We assembled a comprehensive "line-up" of the 36 protein coding loci in the 1.5 Mb minimal critical deleted region on hChr22q11.2, plus 20 protein coding loci in the distal 1.5 Mb that defines the 3 Mb typical 22q11DS deletion. We categorized candidates based upon apparent primary cell biological functions. We analyzed 41 of these genes that encode known proteins to determine whether haploinsufficiency of any single 22q11.2 gene-a one gene to one phenotype correspondence due to heterozygous deletion restricted to that locus-versus complex multigenic interactions can account for single or multiple 22q11DS phenotypes. CONCLUSIONS: Our 22q11.2 functional genomic assessment does not support current theories of single gene haploinsufficiency for one or all 22q11DS phenotypes. Shared molecular functions, convergence on fundamental cell biological processes, and related consequences of individual 22q11.2 genes point to a matrix of multigenic interactions due to diminished 22q11.2 gene dosage. These interactions target fundamental cellular mechanisms essential for development, maturation, or homeostasis at subsets of 22q11DS phenotypic sites. En ligne : https://dx.doi.org/10.1186/s11689-019-9267-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409