<i>
              <scp>ADGRL</scp>
              3 (
              <scp>LPHN</scp>
              3)
            </i>
            variants are associated with a refined phenotype of
            <scp>ADHD</scp>
            in the
            <scp>MTA</scp>
            study

Acosta, Maria T.; Swanson, James M.; Stehli, Annamarie; Molina, Brooke S. G.; Martinez, Ariel F.; Arcos‐Burgos, Mauricio; Muenke, Maximilian

doi:10.1002/mgg3.230

Cited by 36 publications

(19 citation statements)

References 32 publications

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“…Kim et al recently identified that Glis3 could regulate neurogenin-3 expression in pancreatic β-cells [45]. Acosta et al applied experiment and confirmed that Adgrl3 variants are associated with a refined phenotype of attention-deficit/hyperactivity disorder(ADHD) in the MTA study [46]. An ultraconserved brain-specific enhancer in ADGRL3 were reported withADHD susceptibility [47].…”

Section: Resultsmentioning

confidence: 99%

Circular RNA expression profiles during the differentiation of mouse neural stem cells

Yang

Zhao

et al. 2018

BMC Syst Biol

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BackgroundCircular RNAs (circRNAs) have recently been found to be expressed in human brain tissue, and many lines ofevidence indicate that circRNAs play regulatory roles in neurodevelopment. Proliferation and differentiation of neural stem cells (NSCs) are critical parts during development of central nervous system (CNS).To date, there have been no reports ofcircRNA expression profiles during the differentiation of mouse NSCs. We hypothesizethat circRNAs mayregulate gene expression in the proliferation anddifferentiation of NSCs.ResultsIn this study, we obtained NSCs from the wild-type C57BL/6 J mouse fetal cerebral cortex. We extracted total RNA from NSCs in different differentiation stagesand then performed RNA-seq. By analyzing the RNA-Seq data, we found 37circRNAs and 4182 mRNAs differentially expressedduringthe NSC differentiation. Gene Ontology (GO) enrichment analysis of thecognate linear genes of these circRNAsrevealed that some enriched GO terms were related to neural activity. Furthermore, we performed a co-expression network analysis of these differentially expressed circRNAs and mRNAs. The result suggested a stronger GO enrichmentin neural features for both the cognate linear genes of circRNAs and differentially expressed mRNAs.ConclusionWe performed the first circRNA investigation during the differentiation of mouse NSCs. Wefound that12 circRNAs might have regulatory roles duringthe NSC differentiation, indicating that circRNAs might be modulated during NSC differentiation.Our network analysis suggested the possible complex circRNA-mRNA mechanisms during differentiation, and future experimental workis need to validate these possible mechanisms.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0651-1) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Circular RNA expression profiles during the differentiation of mouse neural stem cells

Yang

Zhao

et al. 2018

BMC Syst Biol

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“…Allele calling was made by end-point fluorescent signal analysis using the ABI’s SDS2.3 software. In addition, we had previously collected exome genotype data from the MTA sample 26 using the Infinium ® HumanExome-12 v1.2 BeadChip kit (Illumina), which covers putative functional exonic variants selected from over 12,000 individual exome and whole-genome sequences. Processed and raw intensity signals for the array data can be accessed at GEO (GSE112652).…”

Section: Methodsmentioning

confidence: 99%

“…Using genome-wide data from extended multigenerational families, we found evidence of linkage of ADHD to markers in chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 25 , and co-segregation of ADHD and disruptive behaviors with loci at 2p21-22.3, 4q13.2, 5p13.1-p13.3, 8q24, 8q15, 11q22, 12p11.23-13.3, and 14q21.1-22.2 8 . Fine mapping of the 4q13.2 region identified variants in the adhesion G-protein-coupled receptor L3 gene (ADGRL3 , also known as latrophilin 3 or LPHN3) that predispose to ADHD 22,24,26–30 .…”

Section: Introductionmentioning

confidence: 99%

ADGRL3 (LPHN3) variants predict substance use disorder

et al. 2019

Self Cite

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Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

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“…Genetic factors are strongly implicated in the aetiology of ADHD, CD, ODD, and SUD [6,10,11,12]. In particular, common single nucleotide polymorphisms (SNPs) harboured in the Adhesion G-protein-coupled receptor L3 ( ADGRL3 , also known as Latrophilin 3 or LPHN3 ; markers rs2345039, rs6551665, and rs1947274), the Synaptosomal-associated protein of molecular weight 25 kDa ( SNAP25 ), the Fibroblast growth factor 1 ( FGF1 ), the Solute carrier family 6 (neurotransmitter transporter, noradrenalin) member 2 ( SLC6A2 ), and the Dopamine receptor D4 ( DRD4 ) genes predispose one to ADHD [6,13], as confirmed by worldwide replications [2,3,6,14,15,16,17,18,19,20,21].…”

Section: Introductionmentioning

confidence: 98%

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

Puentes-Rozo

Acosta-López

Cervantes-Henríquez

et al. 2019

Cells

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Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10−4), rs2282794-FGF1 (A allele; p = 1.33 × 10−2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10−2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

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ADGRL 3 ( LPHN 3) variants are associated with a refined phenotype of ADHD in the MTA study

Cited by 36 publications

References 32 publications

Circular RNA expression profiles during the differentiation of mouse neural stem cells

Circular RNA expression profiles during the differentiation of mouse neural stem cells

ADGRL3 (LPHN3) variants predict substance use disorder

Genetic Variation Underpinning ADHD Risk in a Caribbean Community

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