Examination of tetrahydrobiopterin pathway genes in autism.
Autism is a complex disorder with a high degree of heritability and significant phenotypic and genotypic heterogeneity. Although candidate gene studies and genome-wide screens have failed to identify major causal loci associated with autism, numerous studies have proposed association with several variations in genes in the dopaminergic and serotonergic pathways. Because tetrahydrobiopterin (BH4) is the essential cofactor in the synthesis of these two neurotransmitters, we genotyped 25 SNPs in nine genes of the BH4 pathway in a total of 403 families. Significant nominal association was detected in the gene for 6-pyruvoyl-tetrahydropterin synthase, PTS (chromosome 11), with P = 0.009; this result was not restricted to an affected male-only subset. Multilocus interaction was detected in the BH4 pathway alone, but not across the serotonin, dopamine and BH4 pathways.
Schnetz-Boutaud
N C
NC
Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA.
Anderson
B M
BM
Brown
K D
KD
Wright
H H
HH
Abramson
R K
RK
Cuccaro
M L
ML
Gilbert
J R
JR
Pericak-Vance
M A
MA
Haines
J L
JL
D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers; D001708:Biopterins; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase; C003402:sapropterin
Neurogenetics. 2009 Jul;10(3):209-16
19184136
Am J Hum Genet. 2001 Jul;69(1):138-47
11404819
Ann Hum Genet. 2009 May;73(Pt 3):263-73
19456320
Hum Mol Genet. 1999 May;8(5):805-12
10196369
Am J Hum Genet. 2005 Jun;76(6):1050-6
15877280
Mol Psychiatry. 2004 Sep;9(9):819-32
15197396
Am J Hum Genet. 1999 Aug;65(2):493-507
10417292
Arch Neurol. 2003 Jul;60(7):975-80
12873854
Nature. 1977 Feb 24;265(5596):726-8
558516
Am J Hum Genet. 2001 Sep;69(3):570-81
11481586
Autism Res. 2008 Dec;1(6):364-9
19360691
J Child Psychol Psychiatry. 1990 Jan;31(1):39-83
2179248
Am J Hum Genet. 2001 Aug;69(2):269-77
11443547
Am J Hum Genet. 1998 Jul;63(1):259-66
9634505
J Autism Dev Disord. 2003 Aug;33(4):365-82
12959416
Nat Genet. 2007 Mar;39(3):319-28
17322880
J Clin Psychiatry. 2005;66 Suppl 10:3-8
16401144
Am J Hum Genet. 2008 Jan;82(1):160-4
18179894
Biochem J. 2000 Apr 1;347 Pt 1:1-16
10727395
Am J Hum Genet. 2005 Sep;77(3):377-88
16080114
Neurochem Res. 2007 Jan;32(1):107-13
17160504
Am J Hum Genet. 2002 Oct;71(4):777-90
12192642
Chem Rec. 2008;8(6):378-85
19107867
Am J Med Genet. 1994 Dec 15;54(4):318-23
7726203
Am J Hum Genet. 2001 Aug;69(2):327-40
11452361
Bioinformatics. 2005 Jan 15;21(2):263-5
15297300
Am J Med Genet. 1999 Dec 15;88(6):609-15
10581478
Genet Epidemiol. 2007 Nov;31(7):797-800
17654613
N Engl J Med. 2008 Feb 14;358(7):667-75
18184952
Nature. 2009 May 28;459(7246):528-33
19404256
J Clin Psychopharmacol. 2005 Oct;25(5):485-9
16160627
Genet Epidemiol. 2003 Nov;25(3):203-13
14557988
Am J Hum Genet. 2001 Jun;68(6):1514-20
11353400
J Child Psychol Psychiatry. 1990 Jan;31(1):3-37
2179247
Am J Med Genet. 2002 Jan 8;114(1):99-105
11840513
Neurogenetics. 2006 Jul;7(3):167-74
16770606