Review Article

Using Sibling Designs to Understand Neurodevelopmental Disorders: From Genes and Environments to Prevention Programming

Table 1

Summary of individual genes that have been implicated in both ASD and ADHD.

GeneChromosomeFunctionReference
ASDADHD

FMR1 (including premutation) Xq28Involved in making fragile X mental retardation 1 protein (FMRP), an RNA-binding protein involved in gene regulation[150, 151][151153]

TSC2 16p13Actin cytoskeleton dynamics; inactivation of GTPase; neuronal migration and cell differentiation[154156][157, 158]

NF1 17q11Codes for protein neurofibromin and causally related to neurofibromatosis type 1; associated with inactivation of GTPase; cytoskeleton dynamics[159, 160][161]

SHANK3 22q13Dendrite morphology regulation; synapse scaffolding and plasticity; binding neuroligins[162, 163][164]

GRIN2A 16p13Codes for the 2A subunit of the NMDA receptor, which is ligand- and voltage-gated and is involved in long-term potentiation and synaptic transmission [165][134, 166]

GABAR 15q12Encodes the GABA receptors and their subunits, thus mediating neurotransmitter inhibitory processes[167, 168][169, 170]b

SLC6A4/5HTT/SERT 17p11Encodes the serotonin transporter; mediates reuptake of serotonin from synapses[171, 172][173, 174]

SLC6A3/DAT/DAT1 Encodes a dopamine transporter; regulates extracellular dopamine and reuptake of dopamine from synapses[175, 176][177, 178]

OXTR 3p25-26Encodes the oxytocin receptor and thus mediates the action of oxytocin in various brain regions, particularly those supporting social cognition[179, 180][181]a

AVPR1 12q14Encodes the arginine vasopressin receptor 1a, which mediates cell contraction, proliferation, glycogenolysis, and platelet aggregation[182, 183][184]c

SNAP25 20p12-p11.2Encodes a plasma membrane protein involved in vesicle docking, fusion, and neurotransmitter release [185, 186][178, 187]

SLC9A9/NHE9 Encodes a sodium/proton exchanger; plays a role in cation homeostasis[188, 189][190192]

HTR1B 6q13Encodes the 5-HT1B receptor, associated with serotonin regulation; depending on location, it is variably involved in modulating serotonin and dopamine in various cortical and noncortical regions[193][194, 195]

NLGN4 Xp22.3Encodes protein neuroligin 4, involved in cell adhesion, synapse formation, and mediates transsynaptic signalling[196, 197][198, 199]

DRD4 11p15.5Encodes dopamine receptor D4, a G-protein coupled receptor; upon activation, the receptor inhibits adenylyl cyclase, thus decreasing intracellular cyclic AMP[200, 201]d[178, 202]

DRD5 4p16.1Encodes dopamine receptor D5, which is involved in synthesis of cyclic AMP via activation of adenylyl cyclase, and Ca2+ and K+ conductance [203]e[178, 204]

DRD3 3q13.3Encodes dopamine receptor D3; activity is mediated by G-proteins which inhibit adenylyl cyclase; promotes cell proliferation[205, 206][207]

MAOA Xp11.3Encodes enzymes that deaminate and catabolize neurotransmitters such as dopamine, serotonin, and norepinephrine[208210][211, 212]

COMT 22q11.21Encodes the catechol-O-methyltransferase enzyme, which catabolizes neurotransmitters such as dopamine and norepinephrine[213, 214][215, 216]

aFindings should be considered preliminary.
bIn this study, OXTR was only associated with social cognition in ADHD and not diagnostic status itself.
cIn this study, AVPR1A was associated with executive functioning, not ADHD, although executive functioning is considered a core impairment in ADHD (but also other neurodevelopmental conditions, including autism).
dResults may reflect differences in cooccurring symptoms among individuals with ASD as opposed to diagnosis of ASD specifically.
eFew studies have shown similar results, so these should be interpreted cautiously.