Table S1. Overview of family-based (FB) and case-control (CC) association studies with the SLC6A4, 5HT1B and 5HT2A genes in ADHD samples
Gene / Polymorphism / Study design / N / P-value / ADHD sample* / ReferenceSLC6A4
/ 5HTTLPR / CC / 687 cases vs 1013 controls / 0.019 / QTL approach / 1FB / 98 ADHD families / 0.008 / C / 2
CCa / - / 0.008 / C + I + HI / 3
FB / 126 ADHD families / 0036 / 28.6% C + 27.8% I + 7.9 HI + 35.7% NOS / 4
FB / 293 ADHD families / 0.016 / 41.0% C + 52.5% I + 6.5 % HI / 5
CC / 71 cases vs 128 controls / 0.018 / - / 6
CC / 101 cases vs 163 controls / 0.004 / C / 7
FB / 243 families / NS / 65.6% C + 22.4% I + 6.2% HI / 8
FB / 102 ADHD families / NS / 69% C + 27% I + 4 % HI / 9
FB / 46 trios + 9 duos / NS / - / 10
FB / 113 ADHD families / NS / 81% C + 8% I + 11 % HI / 3
FB / 409 ADHD families / NS / 78% C + 22% I / 11
FB / 209 ADHD families / NS / 62% C + 24% I + 14 % HI / 12
FB / 150 trios / NS / - / 13
CC / 150 cases vs 121 controls / NS / - / 13
5HTTVNTR / CC / 46 trios + 5 duos / 0.008b / - / 10
CC / 71 patients vs 128 controls / 0.001 / - / 6
CC / - / NS / C + I + HI / 3
FB / 113 ADHD families / NS / 81% C + 8% I + 11 % HI / 3
FB / 293 ADHD families / NS / 41.0% C + 52.5% I + 6.5 % HI / 5
FB / 150 families / NS / - / 13
CC / 150 cases vs 121 controls / NS / - / 13
CC / 687 cases vs 1013 controls / NS / QTL approach / 1
rs3813034 / FB / 113 ADHD families / 0.04 / 81% C + 8% I + 11 % HI / 3
FB / 209 ADHD families / NS / 62% C + 24% I + 14 % HI / 12
FB / 409 ADHD families / NS / 78% C + 22% I / 11
Ile425Val / FB / 209 ADHD families / NS / 62% C + 24% I + 14 % HI / 12
rs1050565 / CC / 687 cases vs 1013 controls / 0.0045 / QTL approach / 1
rs1487871 / CC / 687 cases vs 1013 controls / 0.033 / QTL approach / 1
rs2020930 / CC / 687 cases vs 1013 controls / 0.035 / QTL approach / 1
rs140701 / CC / 687 cases vs 1013 controls / 0.013 / QTL approach / 1
FB / 674 families / NS / C / 14
rs2020937 / CC / 687 cases vs 1013 controls / 0.027 / QTL approach / 1
rs2020939 / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
rs6354 / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
FB / 674 families / NS / C / 14
rs2020942 / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
FB / 674 families / NS / C / 14
rs1872924 / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
rs140700 / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
FB / 776 ADHD cases / NS / C / 14
3’UTR SNP / CC / 687 cases vs 1013 controls / NS / QTL approach / 1
rs1042173 / FB / 674 families / NSc / C / 14
D17S1294 / FB / 179 families / 0.002d / 77% C + 15% I + 8% HI / 15
5HT1B
/ rs6296 / FB / 273 families / 0.0065 / - / 16FB / 115 families / 0.03d / 57% C + 24% I + 19% HI / 17
FB / 617 families / 0.0009 e / - / 18
FB / 229 families / 0.0056f / 61.5% C + 32.4% I + 6.1% HI / 18
FB / 110 families / NS / 94% C + 6% I / 19
CC / 163 cases vs 129 controls / NS / 94% C + 6% I / 19
FB / 329 dizygotic twins / NS / QTL approach / 20
FB / 358 families / NS / 41% C + 52.5% I + 6.5% HI / 21
FB / 102 ADHD families / NS / 69% C + 27% I + 4 % HI / 9
FB / 203 ADHD families / NS / 60% C + 26% I + 14% HI / 22
FB / 674 families / NS / C / 14
rs6298 / FB / 110 families / NS / 94% C + 6% I / 19
CC / 163 cases vs 129 controls / NS / 94% C + 6% I / 19
FB / 358 families / NS / 41% C + 52.5% I + 6.5% HI / 21
FB / 229 families / NSg / 61.5% C + 32.4% I + 6.1% HI / 18
FB / 203 ADHD families / NSh / 60% C + 26% I + 14% HI / 22
FB / 674 families / NSi / C / 14
5HT2A
/ rs6313 / FB / 195 families / 0.031j / - / 23CC / 323 cases vs 182 controls / 0.003 j / - / 23
FB / 674 families / NS / C / 14
FB / 115 families / NS / - / 24
FB / 102 ADHD families / NS / 69% C + 27% I + 4 % HI / 9
FB / 110 families / NS / 94% C + 6% I / 19
CC / 163 cases vs 129 controls / NS / 94% C + 6% I / 19
CC / 70 cases vs 100 controls / NS / - / 6
rs6314 / FB / 243 families / 0.04k / 65.6% C + 22.4% I + 6.2% HI / 8
FB / 115 families / 0.03 / - / 24
FB / 674 families / NS / C / 14
FB / 102 ADHD families / NS / 69% C + 27% I + 4 % HI / 9
FB / 110 families / NS / 94% C + 6% I / 19
CC / 163 cases vs 129 controls / NS / 94% C + 6% I / 19
FB / 273 families / NS / - / 16
rs6311 / CC / 41 remitted vs 41 non-remitted patients / 0.029l / - / 25
FB / 674 families / NS / C / 14
FB / 243 families / NS / 65.6% C + 22.4% I + 6.2% HI / 8
FB / 102 ADHD families / NS / 69% C + 27% I + 4 % HI / 9
FB / 110 families / NS / 94% C + 6% I / 19
CC / 163 cases vs 129 controls / NS / 94% C + 6% I / 19
CC / 70 cases vs 100 controls / NS / - / 6
rs3803189 / FB / 674 families / NSm / C / 14
* C: Combined ADHD; I: Inattentive ADHD; HI: Hyperactive-Impulsive ADHD
a Case-control data pooled with previously reported datasets from Kent et al., Manor et al. and Seeger et al.
b Preferential maternal transmission was observed (P=0.005).
c Other SNPs were analyzed (rs3794808, rs2054847, rs4583306, rs717742, rs6354, rs2066713, rs2020933), but no association with ADHD was identified.
d When paternal transmission was considered.
e Family-based study with previously reported datasets from Hawi et al., Quist et al. and Smoller et al. Preferential paternal transmission (P=0.00005).
f Over-transmission of the 861G allele to inattentive ADHD offspring (P=0.0056).
g Other SNPs were analyzed (rs130058, rs11568817, rs130060, rs2000292 and rs130056), but no association with ADHD was identified.
h Other SNPs were analyzed (rs6297, rs1213371, rs130058 and rs200292) but no association with ADHD was detected.
i Other SNPs were analyzed (rs9359271, rs2000292, rs6297, rs130060, rs11568817, rs130056, rs1228814, rs4140535, rs1213366), but no association with ADHD was detected.
j When families with affected girls were considered.
k When families with affected boys were considered.
l Association between the –1438A allele and functional remission.
mOther SNPs were analyzed (rs3125, rs7322347, rs1923882, rs977003, rs9567735, rs6561333, rs1923884, rs1923886, rs1745837, rs9316232, rs9316233, rs659734, rs1928042, rs2770296, rs9316235, rs582385, rs1928040, rs731779, rs985934, rs927544, rs9534505, rs4941573, rs1328684, rs6305, rs2296973, rs2070037, rs1328685, rs4142900) but no association with ADHD was identified.
References
1.Curran S, Purcell S, Craig I, Asherson P, Sham P. The serotonin transporter gene as a QTL for ADHD. Am J Med Genet B Neuropsychiatr Genet 2005;134: 42-7.
2.Manor I, Eisenberg J, Tyano S, Sever Y, Cohen H, Ebstein RP, et al. Family-based association study of the serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder. Am J Med Genet 2001;105: 91-5.
3.Kent L, Doerry U, Hardy E, Parmar R, Gingell K, Hawi Z, et al. Evidence that variation at the serotonin transporter gene influences susceptibility to attention deficit hyperactivity disorder (ADHD): analysis and pooled analysis. Mol Psychiatry 2002;7: 908-12.
4.Kim SJ, Badner J, Cheon KA, Kim BN, Yoo HJ, Cook E, Jr., et al. Family-based association study of the serotonin transporter gene polymorphisms in Korean ADHD trios. Am J Med Genet B Neuropsychiatr Genet 2005;139: 14-8.
5.Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, et al. Association between polymorphisms in serotonin transporter gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B Neuropsychiatr Genet 2007;144: 14-9.
6.Zoroglu SS, Erdal ME, Alasehirli B, Erdal N, Sivasli E, Tutkun H, et al. Significance of serotonin transporter gene 5-HTTLPR and variable number of tandem repeat polymorphism in attention deficit hyperactivity disorder. Neuropsychobiology 2002;45: 176-81.
7.Seeger G, Schloss P, Schmidt MH. Functional polymorphism within the promotor of the serotonin transporter gene is associated with severe hyperkinetic disorders. Mol Psychiatry 2001;6: 235-8.
8.Guimaraes AP, Zeni C, Polanczyk GV, Genro JP, Roman T, Rohde LA, et al. Serotonin genes and attention deficit/hyperactivity disorder in a Brazilian sample: preferential transmission of the HTR2A 452His allele to affected boys. Am J Med Genet B Neuropsychiatr Genet 2007;144: 69-73.
9.Heiser P, Dempfle A, Friedel S, Konrad K, Hinney A, Kiefl H, et al. Family-based association study of serotonergic candidate genes and attention-deficit/hyperactivity disorder in a German sample. J Neural Transm 2007;114: 513-21.
10.Banerjee E, Sinha S, Chatterjee A, Gangopadhyay PK, Singh M, Nandagopal K. A family-based study of Indian subjects from Kolkata reveals allelic association of the serotonin transporter intron-2 (STin2) polymorphism and attention-deficit-hyperactivity disorder (ADHD). Am J Med Genet B Neuropsychiatr Genet 2006;141: 361-6.
11.Xu X, Mill J, Chen CK, Brookes K, Taylor E, Asherson P. Family-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: no evidence for association in UK and Taiwanese samples. Am J Med Genet B Neuropsychiatr Genet 2005;139: 11-3.
12.Wigg KG, Takhar A, Ickowicz A, Tannock R, Kennedy JL, Pathare T, et al. Gene for the serotonin transporter and ADHD: no association with two functional polymorphisms. Am J Med Genet B Neuropsychiatr Genet 2006;141: 566-70.
13.Langley K, Payton A, Hamshere ML, Pay HM, Lawson DC, Turic D, et al. No evidence of association of two 5HT transporter gene polymorphisms and attention deficit hyperactivity disorder. Psychiatr Genet 2003;13: 107-10.
14.Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, et al. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 2006;11: 934-53.
15.Hawi Z, Segurado R, Conroy J, Sheehan K, Lowe N, Kirley A, et al. Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. Am J Hum Genet 2005;77: 958-65.
16.Hawi Z, Dring M, Kirley A, Foley D, Kent L, Craddock N, et al. Serotonergic system and attention deficit hyperactivity disorder (ADHD): a potential susceptibility locus at the 5-HT(1B) receptor gene in 273 nuclear families from a multi-centre sample. Mol Psychiatry 2002;7: 718-25.
17.Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R, et al. The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder. Mol Psychiatry 2003;8: 98-102.
18.Smoller JW, Biederman J, Arbeitman L, Doyle AE, Fagerness J, Perlis RH, et al. Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD. Biol Psychiatry 2006;59: 460-7.
19.Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, et al. Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B Neuropsychiatr Genet 2005;134: 67-72.
20.Mill J, Xu X, Ronald A, Curran S, Price T, Knight J, et al. Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B. Am J Med Genet B Neuropsychiatr Genet 2005;133: 68-73.
21.Li J, Wang Y, Zhou R, Zhang H, Yang L, Wang B, et al. Serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder in Chinese Han subjects. Am J Med Genet B Neuropsychiatr Genet 2005;132: 59-63.
22.Ickowicz A, Feng Y, Wigg K, Quist J, Pathare T, Roberts W, et al. The serotonin receptor HTR1B: Gene polymorphisms in attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 2007;144: 121-5.
23.Li J, Wang Y, Qian Q, Wang B, Zhou R. [Association of 5-HT(2A) receptor polymorphism and attention deficit hyperactivity disorder in children]. Zhonghua Yi Xue Za Zhi 2002;82: 1173-6.
24.Quist JF, Barr CL, Schachar R, Roberts W, Malone M, Tannock R, et al. Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 2000;5: 537-41.
25.Li J, Kang C, Wang Y, Zhou R, Wang B, Guan L, et al. Contribution of 5-HT2A receptor gene -1438A>G polymorphism to outcome of attention-deficit/hyperactivity disorder in adolescents. Am J Med Genet B Neuropsychiatr Genet 2006;141: 473-6.
1
Table S2. Description of the 132 SNPs initially selected for the SNPlex analysis within 19 serotoninergic candidate genes for ADHD
1
Gene
/ Contig reference / Location / Length (kp) / Nº of exons / SNPs / Tag SNPs / SNP ID / Location / Exclusion Criteria / Gene Coverage** / Genotype Call Rate / Other SNPs within the BIN5HT1A
NM_000524 / 5q11.2-q13 / 1.268 / 1 / 2 / 1 / rs878567 / 3’ / 1 / 99.3% / rs10042486
5HT1B
NM_000863 / 6q13 / 1.172 / 1 / 3 / 2 / rs130058 / 5’ / 1 / 99.6% / -
rs6296 / Exon 1 / 98.1% / rs6298
5HT1D
NM_000864 / 1p36.3-p34.3 / 2.833 / 1 / 3 / 2 / rs676643 / 5’ / 1 / 98.5% / -
rs604030 / 3’ / 98.6% / rs674386
5HT1E
NM_000865 / 6q14-q15 / 78.986 / 3 / 13 / 8 / rs828358 / Intron 1 / 0.71 / 99.4% / -
rs10944288 / Intron 1 / In LD with other SNPs* / -
rs2325017 / Intron 1 / No SNPlex design / -
rs1581774 / Intron 2 / 99.5% / -
rs1408449 / Intron 2 / 98.7% / -
rs942472 / Intron 2 / Genotyping Failure / <90% / -
rs2209639 / Intron 2 / 98.4% / rs6935195, rs13340450, rs1886333, rs16878041, rs11964445
rs9344666 / 3’ / 98.7% / -
5HT1F
NM_000866 / 3p12 / 1.100 / 1 / 2 / 1 / rs1503433 / 5’ / 1 / 99.1% / rs2016224
5HT2A
NM_000621 / 13q14-q21 / 62.662 / 3 / 51+1 / 24 / rs17289394 / 5’ / In LD with other SNPs* / 0.90 / -
rs2070040 / Intron 1 / 98.6% / -
rs9534511 / Intron 1 / 99.5% / -
rs2296973 / Intron 1 / 99.6% / -
rs1328684 / Intron 2 / 98.9% / -
rs2770304 / Intron 2 / 99.3% / -
rs9526246 / Intron 2 / In LD with other SNPs* / rs732821, rs731245, rs6311, rs6313, rs4941573, rs6561336, rs1928040
rs1410657 / Intron 2 / 97.3% / rs985933, rs985934, rs972979
rs2770296 / Intron 2 / 99.5% / rs2770298
rs4941570 / Intron 2 / 98.5% / -
rs2770293 / Intron 2 / 98.6% / -
rs6561335 / Intron 2 / 98.7% / -
rs2224721 / Intron 2 / 99.6% / -
rs2760351 / Intron 2 / Genotyping Failure / <90% / -
rs1885884 / Intron 2 / Genotyping Failure / <90% / -
rs7984966 / Intron 2 / 99.9% / -
rs9534495 / Intron 2 / 99.3% / -
rs2770300 / Intron 2 / 97.5% / rs643627, rs2296972, rs655854, rs655888, rs621494, rs622337, rs632903, rs1745837
rs1923887 / Intron 2 / 98.7% / rs9316232, rs9567739
rs6561333 / Intron 2 / 98.5% / rs1923886, rs9567737
rs6561332 / Intron 2 / 99.5% / rs7330636, rs7330461, rs1923885
rs7997012 / Intron 2 / 98.5% / -
rs7322347 / Intron 2 / 98.4% / rs977003
rs1058576 / Exon 3 / Monomorphic
5HT2B
NM_000867 / 2q37.1 / 16.869 / 4 / 5 / 4 / rs6437000 / Intron 3 / Genotyping Failure / 0.75 / <90% / rs1549339
rs10194776 / Intron 2 / 99.9% / -
rs16827801 / Intron 2 / 99.8% / -
rs4973377 / Intron 2 / 98.8% / -
5HT2C
NM_000868 / Xq24 / 326.073 / 6 / 68+1 / 9 / rs475717 / 5’ / 0.75 / 98.8% / rs543229, rs539748, rs556677, rs12558624, rs6579490, rs17326436, rs2041675, rs7881868, rs5987797, rs7890593, rs2069237, rs5987801, rs7877304, rs5987802, rs5988087, rs11167435, rs11167436, rs6643889, rs5987810, rs5988105, rs2497551, rs2248440, rs2497548, rs2497542, rs2497540, rs2497538, rs2497537, rs2428722, rs2497535, rs2428716
rs3813928 / 5’ / MAF<0.15* / rs12688871, rs3795182, rs17260565, rs17326429, rs11798460, rs12846241, rs12837651, rs11797955, rs12860460, rs12690355
rs518147 / Exó 1 / 99.2% / rs478209, rs547536, rs539023, rs498207, rs569959, rs498177, rs12838742, rs9698290, rs7055144, rs7887868, rs2192371, rs5988072, rs11798698, rs12847225, rs7890739, rs12688102
rs6579495 / Intron 2 / 97.9% / rs12855702
rs6318 / Exon 4 / 99.1%
rs2428721 / Intron 4 / 98.4% / rs2428720
rs4911871 / Intron 4 / 98.2% / rs6643897, rs12381959
rs2497503 / Intron 4 / MAF<0.15* / -
rs4537474 / Intron 4 / No SNPlex design / -
5HT3A
NM_000869 / 11q23.1 / 15.122 / 9 / 12 / 4 / rs1150222 / Intron 1 / 1 / 99.5% / rs1176722, rs1176720, rs10891611, rs948983, rs1182457
rs1985242 / Intron 1 / 99.6% / rs2276302
rs1176717 / Intron 5 / 99.4% / rs11214796, rs1176713
rs10160548 / Intron 5 / 99.5% / -
5HT3B
NM_006028 / 11q23.1 / 41.693 / 9 / 17 / 9 / rs11214763 / 5’ / 0.75 / 99.2% / rs7943062, rs7945926
rs12270070 / Intron 2 / 97.6% / rs2276307, rs4938059
rs1176746 / Intron 4 / No SNPlex design / -
rs1176744 / Exon 5 / 99.6% / rs3758987, rs11214769
rs1176743 / Intron 6 / In LD with other SNPs* / rs7103572
rs11214775 / Intron 6 / 99.6% / -
rs3782025 / Intron 6 / Genotyping Failure / <90% / -
rs1672717 / Intron 6 / 98.5% / rs1185027
rs7129190 / 3’ / 98.6% / -
5HT4
NM_199453 / 5q31-q33 / 185.850 / 7 / 87 / 17 / rs6865654 / Intron 1 / 0.88 / 99.9% / rs10477387
rs9686886 / Intron 1 / 98.2% / -
rs7721747 / Intron 1 / 99.3% / rs6580561, rs11956922, rs2068190
rs10223307 / Intron 1 / 98.1% / rs5028114, rs7701432
rs7711800 / Intron 1 / 98.6% / -
rs2910098 / Intron 1 / 94.5% / rs10078551, rs13166230, rs13165109, rs13182913, rs6580558, rs1816067, rs11955434, rs13159629, rs2964276, rs980062
rs888957 / Intron 1 / No SNPlex design / -
rs1820071 / Intron 1 / No SNPlex design / -
rs6873382 / Intron 1 / 98.1% / rs4343830, rs1833708, rs1345697, rs7718022, rs1363545
rs13166761 / Intron 1 / 98.7% / rs4336354, rs17777511, rs7715569, rs7726693, rs17108421, rs13173317, rs1820075, rs17720660, rs2895768, rs1368391, rs13159589, rs17777298, rs12152801, rs13173328, rs13179862, rs1973878
rs10515616 / Intron 1 / In LD with other SNPs* / rs17720691
rs1368384 / Intron 4 / 98.2% / rs1422636
rs2005953 / Intron 5 / 99.3% / rs9325104, rs891962, rs6580555, rs1432913, rs1368388, rs1368386, rs13154725, rs7723153, rs1883074
rs4597955 / Intron 5 / 99.3% / -
rs3995090 / Intron 5 / 98.6% / rs7733088, rs11168049, rs6887366, rs3995091, rs1985524, rs6889822, rs7735184, rs11168048, rs10463406
rs13156542 / Intron 6 / 98.5% / rs10037493, rs12717975, rs12374521
rs4274967 / 3’ / 99.9% / rs2037997, rs7733401, rs7727320, rs7727161, rs1971431, rs1984789, rs9325098, rs6884076, rs4274968, rs4574533
5HT5A
NM_024012 / 7q36.1 / 13.587 / 2 / 14 / 7 / rs1800883 / 5’ / No SNPlex design / 0.71 / -
rs6320 / Exon 1 / 98.5% / -
rs2241859 / Intron 1 / 99.8% / -
rs2581841 / Intron 1 / 99.9% / rs1079515, rs2581838, rs731107, rs732050, rs1657269, rs1730208, rs1631327
rs6597455 / Intron 1 / 98.4% / -
rs1657268 / Intron 1 / 98.2% / -
rs1440449 / Intron 1 / No SNPlex design / -
5HT6
NM_000871 / 1p35-p36 / 14.275 / 3 / 2 / 2 / rs4912138 / Intron 1 / 1 / 98.4% / -
rs9659997 / Intron 1 / 97.8% / -
5HT7
NM_019859 / 10q21-q24 / 117.093 / 4 / 53 / 11 / rs1298056 / 3’ / 0.8 / 98.2% / rs11596518, rs11599921, rs11592512, rs3740046
rs11817364 / 3’ / 98.4% / rs4933195, rs1935351, rs11594548, rs12766851, rs11186309, rs4272713, rs12412496, rs4933607, rs7091039, rs7086484, rs7072526, rs7912164, rs11812708
rs1274446 / 3’ / Not in HWE* / rs7919103, rs6583736, rs7082558, rs10881832, rs7476323, rs2420367, rs11186300, rs7916848, rs4933194, rs1935347, rs11186297
rs7904560 / Intron 1 / 99.1% / -
rs7916403 / Intron 1 / 98.6% / rs1573935
rs11186320 / Intron 1 / 98.6% / rs4520504, rs11599902, rs11597471, rs12259401, rs10785972, rs10881838, rs7087400
rs12261011 / Intron 1 / MAF<0.15* / rs11186341, rs11186338,rs12264160, rs12249377, rs12246118
rs10785973 / Intron 1 / 99.8% / -
rs2226116 / Intron 1 / MAF<0.15* / -
rs7084468 / Intron 1 / 98.5% / -
rs12259062 / Intron 1 / 98.1% / rs12254390
SLC6A4
NM_001045 / 17q11.1-q12 / 377.99 / 15 / 16+1 / 5 / rs12150214 / Intron 1 / No SNPlex design / 0.5 / rs8071667, rs2020936, rs25528, rs6354
rs2020942 / Intron 3 / 98.6% / rs2066713
rs2228673 / Exon 5 / Monomorphic
rs140701 / Intron 9 / 99.4% / -
rs11080121 / Intron 14 / Genotyping Failure / <90% / rs2020939, rs4583306, rs2054847, rs3794808, rs1042173, rs3813034, rs7224199
DDC
NM_000790 / 7p11 / 102.615 / 15 / 74 / 15 / rs7803788 / Intron 1 / 0.85 / 98.6% / rs7807335, rs10265930, rs10249420
rs2329340 / Intron 1 / 99.2% / rs1966839, rs921451, rs921450, rs1451374, rs1451373, rs6962356, rs6949897, rs10250513, rs2329341
rs10499695 / Intron 1 / 98.9% / -
rs11974297 / Intron 1 / 98.6% / rs10278338, rs6593010, rs3829897, rs6969081
rs10499694 / Intron 1 / In LD with other SNPs* / rs4947644, rs11765748, rs7786398, rs998850, rs11575334
rs2044859 / Intron 1 / 99.4% / -
rs1982406 / Intron 4 / 99.1% / rs10244632
rs7809758 / Intron 6 / No SNPlex design / rs2198144, rs1817074, rs4947584, rs2167364, rs1037351
rs6944090 / Intron 6 / 99.3% / rs3735274, rs12690481, rs11238178, rs2100280
rs6592961 / Intron 6 / 99.3% / -
rs3823674 / Intron 6 / In LD with other SNPs* / -
rs2876827 / Intron 10 / No SNPlex design / rs6592952, rs1451372, rs2122822, rs12718541, rs11980368, rs13311361, rs4947577, rs11575457, rs10899734, rs1349492, rs4579483, rs4579483, rs4433100, rs4329234, rs11238138, rs12718529, rs12718528, rs4992502, rs2329365, rs7803247, rs730092
rs732215 / Intron 11 / 98.6% / rs1470750, rs12718574, rs12718572, rs1451371, rs10899736
rs11761683 / Intron 11 / 98.7% / rs11238133
rs11238131 / Intron 11 / 99.3% / rs7785224, rs4947535
MAOA
NM_000240 / Xp11.3 / 90.658 / 15 / 14 / 2 / rs3027400 / Intron 9 / 1 / 98.6% / rs3027401, rs2235186, rs2235185, rs2205718, rs979606, rs979605, rs2239448, rs1801291, rs3027407, rs3027410, rs2064070
rs2072743 / Intron 10 / 99.2% / rs2072744
MAOB
NM_000898 / Xp11.23 / 115.823 / 15 / 10 / 5 / rs5906213 / 5’ / 0.8 / 98.7% / -
rs5905512 / Intron 1 / 98.7% / -
rs10521432 / Intron 12 / Not in HWE* / rs6651806, rs2283729, rs3027456
rs1799836 / Intron 13 / 99.1% / -
rs3027415 / 3’ / 98.7% / rs5905449, rs3027450
TPH1
NM_004179 / 11p15.3-p14 / 19.771 / 10 / 15 / 4 / rs10488683 / Intron 3 / 0.75 / 99.3% / -
rs172423 / Intron 2 / 97.6% / rs10488682, rs10832876, rs11024449
rs1800532 / Intron 6 / 99.3% / rs508924, rs685657, rs684302, rs169806, rs211107, rs2056246, rs1607395, rs10741734
rs211102 / Intron 7 / MAF<0.15* / rs591556
1
*As assessed in the sample of 400 controls; ** Analyzed tagSNPs/total tagSNPs within the gene.
1
Table S3. Assessment of population stratification using 45 unlinked SNPs in HWE with the STRUCTURE software.
Number of subpopulations (K) / LnP(D)* / Var[Ln(P)]** /Posterior probability of K***
1 / -47465.9 / 0.15 / 0.9992 / -47732.8 / 58.14 / 1.15e-116
3 / -47977.1 / 62.55 / 9.74e-223
4 / -47893.1 / 196.14 / 2.78e-186
5 / -47759.7 / 305.72 / 1.88e-128
* Ln of the probability of the data, calculated as an average of 5 independent iterations, with burning period and number of MCMC repeats after burning set to 100,000. An admixture ancestry model with correlated allele frequencies (=1) was assumed; ** Variance of the four LnP(D) iterations;*** Calculated using Bayes’ rule.
1
Table S4. Nominal P-values observed when genotype and allele frequencies of 100 SNPs within 19 candidate genes were considered in 188 adults with ADHD, 263 children with ADHD and 400 controls
Adults
/Children
ADHD (n=188) / Combined ADHD (n=126) / Inattentive ADHD (n=55) / ADHD (n=263) / Combined ADHD (n=192) / Inattentive ADHD (n=58)Gene
/SNP
/Genotypes
/ Alleles /Genotypes
/ Alleles / Genotypes / Alleles / Genotypes / Alleles / Genotypes / Alleles /Genotypes
/ Alleles5HT1A / rs878567 / 0.63 / 0.39 / 0.59 / 0.32 / 0.93 / 0.71 / 0.71 / 0.43 / 0.74 / 0.44 / 0.45 / 0.22
5HT1B / rs130058 / 0.72 / 0.92 / 0.83 / 0.93 / 0.65 / 0.73 / 0.86 / 0.60 / 0.89 / 0.92 / 0.47 / 0.47
rs6296 / 0.80 / 0.70 / 0.85 / 0.86 / 0.31 / 0.13 / 0.033 / 0.52 / 0.015 / 0.83 / 0.59 / 0.62
5HT1D / rs676643 / 0.94 / 0.80 / 0.55 / 0.83 / 0.93 / 0.85 / 0.23 / 0.11 / 0.55 / 0.37 / 0.14 / 0.045
rs604030 / 0.62 / 0.71 / 0.57 / 0.66 / 1.00 / 0.98 / 0.046 / 0.038 / 0.07 / 0.039 / 0.20 / 0.20
5HT1E / rs828358 / 0.82 / 0.65 / 0.93 / 0.81 / 0.35 / 0.16 / 0.30 / 0.53 / 0.08 / 0.46 / 0.92 / 0.70
rs1581774 / 0.88 / 0.80 / 0.59 / 0.69 / 0.18 / 0.16 / 0.93 / 0.71 / 0.95 / 0.82 / 0.85 / 0.58
rs1408449 / 0.41 / 0.59 / 0.43 / 0.56 / 0.93 / 0.75 / 0.82 / 0.54 / 0.92 / 0.79 / 0.48 / 0.26
rs2209639 / 0.68 / 0.47 / 0.52 / 0.85 / 0.23 / 0.36 / 0.70 / 0.72 / 0.49 / 0.76 / 0.79 / 0.79
rs9344666 / 0.56 / 0.29 / 0.73 / 0.73 / 0.19 / 0.08 / 0.51 / 0.43 / 0.30 / 0.13 / 0.26 / 0.31
5HT1F / rs1503433 / 0.10 / 0.67 / 0.60 / 0.81 / 0.023 / 0.20 / 0.20 / 0.47 / 0.44 / 0.54 / 0.48 / 0.53
5HT2A / rs2070040 / 0.76 / 0.64 / 0.39 / 0.18 / 0.81 / 0.55 / 0.73 / 0.67 / 0.85 / 0.83 / 0.35 / 0.31
rs9534511 / 0.25 / 0.94 / 0.36 / 0.52 / 0.64 / 0.66 / 0.23 / 0.76 / 0.30 / 0.79 / 0.15 / 0.24
rs2296973 / 0.65 / 0.54 / 0.98 / 0.84 / 0.10 / 0.20 / 0.12 / 0.97 / 0.14 / 0.87 / 0.60 / 0.55
rs1328684 / 0.18 / 0.27 / 0.049 / 0.19 / 0.84 / 0.63 / 0.16 / 0.67 / 0.13 / 0.19 / 0.17 / 0.33
rs2770304 / 0.91 / 0.68 / 0.38 / 0.18 / 0.33 / 0.22 / 0.15 / 0.47 / 0.23 / 0.74 / 0.40 / 0.21
rs1410657 / 0.99 / 0.89 / 0.76 / 0.47 / 0.46 / 0.25 / 0.70 / 0.59 / 0.89 / 0.89 / 0.45 / 0.21
rs2770296 / 0.70 / 0.40 / 0.12 / 0.037 / 0.59 / 0.30 / 0.58 / 0.56 / 0.79 / 0.90 / 0.35 / 0.31
rs4941570 / 0.72 / 0.65 / 0.30 / 0.19 / 0.84 / 0.57 / 0.97 / 0.91 / 0.85 / 0.58 / 0.59 / 0.50
rs2770293 / 0.37 / 0.58 / 0.31 / 0.16 / 0.57 / 0.83 / 0.48 / 0.93 / 0.53 / 0.62 / 0.16 / 0.16
rs6561335 / 0.61 / 0.92 / 0.70 / 0.43 / 0.24 / 0.24 / 0.19 / 0.87 / 0.24 / 0.91 / 0.18 / 0.53
rs2224721 / 0.08 / 0.24 / 0.019 / 0.08 / 0.65 / 0.59 / 0.23 / 0.29 / 0.43 / 0.22 / 0.30 / 0.33
rs7984966 / 0.07 / 0.024 / 0.004 / 0.002 / 0.21 / 0.69 / 0.07 / 0.039 / 0.021 / 0.011 / 0.93 / 0.82
rs9534495 / 0.10 / 0.043 / 0.016 / 0.005 / 0.95 / 0.94 / 0.50 / 0.50 / 0.29 / 0.17 / 0.22 / 0.49
rs2770300 / 0.70 / 0.54 / 0.33 / 0.28 / 0.89 / 0.66 / 0.16 / 0.07 / 0.05 / 0.06 / 0.63 / 0.41
rs1923887 / 0.89 / 0.80 / 0.67 / 0.55 / 0.96 / 0.77 / 0.16 / 0.08 / 0.046 / 0.11 / 0.24 / 0.29
rs6561333 / 0.33 / 0.19 / 0.20 / 0.16 / 0.92 / 0.67 / 0.33 / 0.13 / 0.05 / 0.011 / 0.37 / 0.22
rs6561332 / 0.15 / 0.86 / 0.40 / 0.91 / 0.14 / 0.94 / 0.29 / 0.10 / 0.048 / 0.010 / 0.52 / 0.30
rs7997012 / 0.79 / 0.79 / 0.60 / 0.90 / 0.86 / 0.57 / 0.05 / 0.024 / 0.021 / 0.004 / 0.07 / 0.87
rs7322347 / 0.045 / 0.30 / 0.039 / 0.13 / 0.29 / 0.79 / 0.033 / 0.008 / 0.009 / 0.0015 / 0.18 / 0.96
5HT2B / rs10194776 / 0.89 / 0.70 / 0.57 / 0.37 / 0.78 / 0.53 / 0.86 / 0.71 / 0.95 / 0.94 / 0.83 / 0.56
rs16827801 / 0.93 / 0.90 / 0.76 / 0.55 / 0.80 / 0.53 / 0.86 / 0.61 / 0.86 / 0.75 / 0.73 / 0.70
rs4973377 / 0.62 / 0.96 / 0.26 / 0.73 / 0.26 / 0.84 / 0.15 / 0.82 / 0.35 / 0.88 / 0.10 / 0.78
5HT2C / rs475717 / 0.58 / 0.11 / 0.48 / 0.09 / 0.9 / 0.51 / 0.59 / 0.89 / 0.97 / 0.55 / 0.14 / 0.15
rs518147 / 0.32 / 0.09 / 0.32 / 0.049 / 0.57 / 0.58 / 0.40 / 0.27 / 0.69 / 0.57 / 0.26 / 0.08
rs6579495 / 0.51 / 0.17 / 0.64 / 0.14 / 0.52 / 0.57 / 0.46 / 0.85 / 0.81 / 0.65 / 0.34 / 0.49
rs6318 / 0.55 / 0.11 / 0.2 / 0.11 / 0.88 / 0.45 / 0.78 / 0.47 / 0.94 / 0.26 / 0.22 / 0.88
rs2428721 / 0.74 / 0.21 / 0.14 / 0.41 / 0.25 / 0.27 / 0.67 / 0.68 / 0.66 / 0.26 / 0.96 / 0.41
rs4911871 / 0.2 / 0.58 / 0.21 / 0.39 / 0.52 / 0.96 / 0.29 / 0.96 / 0.52 / 0.80 / 0.82 / 0.90
5HT3A / rs1150222 / 0.07 / 0.15 / 0.53 / 0.54 / 0.018 / 0.05 / 0.36 / 0.34 / 0.46 / 0.20 / 0.06 / 0.63
rs1985242 / 0.21 / 0.49 / 0.50 / 0.97 / 0.031 / 0.046 / 0.38 / 0.61 / 0.33 / 1.00 / 0.46 / 0.20
rs1176717 / 0.88 / 0.76 / 0.72 / 0.52 / 0.07 / 0.08 / 0.30 / 0.29 / 0.35 / 0.15 / 0.06 / 0.74
5HT3B / rs11214763 / 0.59 / 0.36 / 0.64 / 0.37 / 0.60 / 0.42 / 0.63 / 0.64 / 0.67 / 0.73 / 0.94 / 0.89
rs10160548 / 0.70 / 0.77 / 0.40 / 0.22 / 0.43 / 0.28 / 0.86 / 0.70 / 0.93 / 0.81 / 0.71 / 0.51
rs12270070 / 0.78 / 0.57 / 0.73 / 0.80 / 0.87 / 0.98 / 0.79 / 0.64 / 0.57 / 0.31 / 0.78 / 0.54
rs1176744 / 0.38 / 0.34 / 0.43 / 0.22 / 0.73 / 0.73 / 0.50 / 0.37 / 0.57 / 0.37 / 0.93 / 0.97
rs11214775 / 0.55 / 0.97 / 0.55 / 0.62 / 0.37 / 0.27 / 0.55 / 0.29 / 0.39 / 0.23 / 0.51 / 0.99
rs1672717 / 0.14 / 0.35 / 0.017 / 0.12 / 0.64 / 0.49 / 0.98 / 0.85 / 0.75 / 0.52 / 0.58 / 0.56
rs7129190 / 0.33 / 0.79 / 0.27 / 0.88 / 0.86 / 0.59 / 0.81 / 0.94 / 0.90 / 0.77 / 0.81 / 0.99
5HT4 / rs6865654 / 0.93 / 0.74 / 0.52 / 0.26 / 0.45 / 0.30 / 0.66 / 0.37 / 0.67 / 0.44 / 0.58 / 0.82
rs9686886 / 0.88 / 0.66 / 0.66 / 0.35 / 0.77 / 0.51 / 0.57 / 0.86 / 0.78 / 0.86 / 0.59 / 0.56
rs7721747 / 0.77 / 0.50 / 0.55 / 0.40 / 0.66 / 0.71 / 0.38 / 0.16 / 0.58 / 0.34 / 0.25 / 0.60
rs10223307 / 0.73 / 0.87 / 0.45 / 0.52 / 0.98 / 0.95 / 0.41 / 0.36 / 0.73 / 0.67 / 0.18 / 0.50
rs7711800 / 0.34 / 0.42 / 0.49 / 0.41 / 0.37 / 0.97 / 0.61 / 0.82 / 0.86 / 0.78 / 0.30 / 0.88
rs2910098 / 0.95 / 0.97 / 1.00 / 0.92 / 0.60 / 0.84 / 0.39 / 0.70 / 0.41 / 0.72 / 0.84 / 0.60
rs6873382 / 0.52 / 0.40 / 0.72 / 0.41 / 0.24 / 0.52 / 0.20 / 0.11 / 0.26 / 0.13 / 0.59 / 0.84
rs13166761 / 0.22 / 0.85 / 0.43 / 0.69 / 0.37 / 0.83 / 0.35 / 0.83 / 0.52 / 0.85 / 0.78 / 0.56
rs1368384 / 0.93 / 0.74 / 0.86 / 0.81 / 0.51 / 0.25 / 0.87 / 0.62 / 0.85 / 0.59 / 0.85 / 0.67
rs2005953 / 0.71 / 0.51 / 0.71 / 0.41 / 0.37 / 0.85 / 0.15 / 0.33 / 0.10 / 0.36 / 0.93 / 0.92
rs4597955 / 0.32 / 0.14 / 0.36 / 0.27 / 0.28 / 0.13 / 0.68 / 0.51 / 0.44 / 0.34 / 0.90 / 0.67
rs3995090 / 0.78 / 0.51 / 0.68 / 0.45 / 0.60 / 0.51 / 0.32 / 0.73 / 0.27 / 0.56 / 0.53 / 0.59
rs13156542 / 0.22 / 0.19 / 0.11 / 0.22 / 0.39 / 0.18 / 0.47 / 0.99 / 0.42 / 0.60 / 0.49 / 0.30
rs4274967 / 0.39 / 0.56 / 0.35 / 0.65 / 0.83 / 0.56 / 0.27 / 0.30 / 0.29 / 0.53 / 0.57 / 0.32
5HT5A / rs6320 / 0.81 / 0.69 / 0.13 / 0.29 / 0.10 / 0.44 / 0.88 / 0.91 / 0.65 / 0.36 / 0.30 / 0.14
rs2241859 / 0.82 / 0.72 / 0.71 / 0.65 / 0.93 / 0.70 / 0.63 / 0.47 / 0.85 / 0.67 / 0.10 / 0.06
rs2581841 / 0.93 / 0.80 / 0.94 / 0.98 / 0.65 / 0.35 / 0.45 / 0.34 / 0.55 / 0.54 / 0.15 / 0.07
rs6597455 / 0.53 / 0.28 / 0.56 / 0.28 / 0.93 / 1.00 / 0.75 / 0.60 / 0.86 / 0.84 / 0.33 / 0.18
rs1657268 / 0.58 / 0.72 / 0.52 / 0.56 / 0.76 / 0.51 / 0.43 / 0.82 / 0.46 / 0.90 / 0.66 / 0.51
5HT6 / rs4912138 / 0.23 / 0.09 / 0.44 / 0.20 / 0.54 / 0.31 / 0.96 / 0.86 / 0.86 / 0.66 / 0.50 / 0.26
rs9659997 / 0.026 / 0.005 / 0.17 / 0.05 / 0.08 / 0.031 / 0.34 / 0.65 / 0.63 / 0.72 / 0.12 / 0.91
5HT7 / rs1298056 / 0.69 / 0.40 / 0.66 / 0.39 / 1.00 / 0.94 / 0.61 / 0.41 / 0.53 / 0.55 / 0.87 / 0.70
rs11817364 / 0.07 / 0.024 / 0.026 / 0.06 / 0.06 / 0.09 / 0.15 / 0.07 / 0.14 / 0.06 / 0.81 / 0.52
rs7904560 / 0.20 / 0.06 / 0.33 / 0.12 / 0.67 / 0.37 / 0.06 / 0.72 / 0.05 / 0.87 / 0.71 / 0.77
rs7916403 / 0.51 / 0.80 / 0.90 / 0.68 / 0.06 / 0.77 / 0.22 / 0.08 / 0.38 / 0.16 / 0.37 / 0.18
rs11186320 / 0.025 / 0.005 / 0.023 / 0.008 / 0.07 / 0.11 / 0.23 / 0.15 / 0.28 / 0.13 / 0.47 / 0.40
rs10785973 / 0.76 / 0.67 / 0.84 / 0.56 / 0.20 / 0.65 / 0.67 / 0.43 / 0.52 / 0.24 / 0.64 / 0.97
rs7084468 / 0.75 / 0.70 / 0.24 / 0.47 / 0.36 / 0.87 / 0.89 / 0.74 / 0.97 / 0.98 / 0.22 / 0.08
rs12259062 / 0.17 / 0.05 / 0.07 / 0.048 / 0.19 / 0.31 / 0.47 / 0.21 / 0.53 / 0.26 / 0.45 / 0.21
SLC6A4 / rs2020942 / 0.26 / 0.50 / 0.57 / 0.71 / 0.49 / 0.57 / 0.92 / 0.74 / 0.78 / 0.57 / 0.85 / 0.65
rs140701 / 0.46 / 0.41 / 0.41 / 0.21 / 0.74 / 0.70 / 0.94 / 0.99 / 0.53 / 0.82 / 0.36 / 0.31
DDC / rs7803788 / 0.20 / 0.29 / 0.15 / 0.08 / 0.29 / 0.32 / 0.36 / 0.18 / 0.32 / 0.16 / 0.65 / 0.56
rs2329340 / 0.07 / 0.66 / 0.16 / 0.81 / 0.08 / 0.13 / 0.99 / 0.98 / 0.94 / 0.76 / 0.69 / 0.94
rs10499695 / 0.97 / 0.82 / 0.87 / 0.61 / 0.79 / 0.54 / 0.36 / 0.75 / 0.19 / 0.46 / 0.44 / 0.28
rs11974297 / 0.16 / 0.85 / 0.13 / 0.78 / 0.39 / 0.32 / 0.59 / 0.36 / 0.62 / 0.45 / 0.82 / 0.81
rs2044859 / 0.29 / 0.34 / 0.22 / 0.23 / 0.68 / 0.62 / 0.82 / 0.56 / 0.95 / 0.83 / 0.16 / 0.07
rs1982406 / 0.18 / 0.24 / 0.033 / 0.11 / 0.72 / 0.71 / 0.017 / 0.009 / 0.0024 / 0.0031 / 0.97 / 0.84
rs6944090 / 0.40 / 0.40 / 0.12 / 0.28 / 0.57 / 0.87 / 0.16 / 0.15 / 0.06 / 0.08 / 0.77 / 0.46
rs6592961 / 0.002 / 0.003 / 0.003 / 0.002 / 0.31 / 0.34 / 1e-05 / 2e-05 / 0.00027 / 0.0005 / 0.0028 / 0.0014
rs732215 / 0.25 / 0.13 / 0.27 / 0.16 / 0.59 / 0.31 / 0.08 / 0.07 / 0.06 / 0.039 / 0.53 / 0.97
rs11761683 / 0.15 / 0.53 / 0.11 / 0.82 / 0.19 / 0.10 / 0.94 / 0.78 / 0.92 / 0.76 / 0.47 / 0.32
rs11238131 / 0.80 / 0.51 / 0.94 / 0.78 / 0.50 / 0.27 / 0.38 / 0.74 / 0.47 / 0.74 / 0.49 / 0.63
TPH1 / rs10488683 / 0,91 / 0,74 / 0,89 / 0,64 / 0,95 / 0,88 / 0,90 / 0,64 / 0,92 / 0,76 / 0,63 / 0,36
rs172423 / 0,32 / 0,26 / 0,30 / 0,16 / 0,80 / 1,00 / 0,42 / 0,38 / 0,29 / 0,19 / 0,88 / 0,88
rs1800532 / 0,57 / 0,67 / 0,33 / 0,25 / 0,62 / 0,49 / 0,14 / 0,11 / 0,053 / 0,030 / 0,93 / 0,87
MAOA / rs3027400 / 0.72 / 0.24 / 0.15 / 0.08 / 0.94 / 0.96 / 0.87 / 0.50 / 0.97 / 0.89 / 0.76 / 0.22
rs2072743 / 0.96 / 0.86 / 0.64 / 0.44 / 0.58 / 0.49 / 0.46 / 0.40 / 0.17 / 0.63 / 0.48 / 0.10
MAOB / rs5906213 / 0,54 / 0,25 / 0,91 / 0,73 / 0,32 / 0,13 / 0,29 / 0,96 / 0,52 / 0,80 / 0,82 / 0,90
rs5905512 / 0,20 / 0,16 / 0,11 / 0,25 / 0,60 / 0,40 / 0,67 / 0,68 / 0,66 / 0,26 / 0,96 / 0,41
rs1799836 / 0,16 / 0,08 / 0,37 / 0,25 / 0,18 / 0,13 / 0,46 / 0,85 / 0,81 / 0,65 / 0,34 / 0,49
rs3027415 / 0,015 / 0,00056 / 0,09 / 0,011 / 0,041 / 0,0055 / 0,78 / 0,47 / 0,94 / 0,26 / 0,22 / 0,88
Table S5. (a) Haplotype analysis of 11 DDC SNPs in a clinical sample of 126 adult combined ADHD patients, 192 child combined ADHD patients and 400 controls using the
UNPHASED software; (b) Haplotype distributions of the rs11238131, rs6592961, rs1982406 and rs2044859 DDC SNPs
(a)
Adults / Children / Adults + Children**Marker * haplotype / Global P-value / Best haplotype-specific P-value (Adjusted P-value) / Haplotype- specific OR (CI) / Global P-value / Best haplotype-specific P-value (Adjusted P-value) / Haplotype- specific OR (CI) / Global P-value / Best haplotype-specific P-value (Adjusted P-value) / Haplotype- specific OR (CI)
1 4 / 0.0016 / 0.0011 (0.007) / 2.56 (1.62-4.03) / 0.0090 / 0.0076 (0.0318) / 1.55 (1.06-2.27) / 0.00030 / 0.00023 (0.0014) / 2.03 (1.40-2.95)
1 4 6 / 0.0016 / 0.0032 (0.025) / 2.48 (1.52-4.03) / 0.00065 / 0.0011 (0.0078) / 1.88 (1.27-2.77) / 0.00017 / 0.00027 (0.0027) / 1.74 (1.23-2.46)
1 4 6 7 / 0.016 / 0.002 ()0.016) / 2.25 (1.39-3.64) / 0.026 / 0.0045 (0.024) / 1.90 (1.23-2.93) / 0.0021 / 0.00013 (0.0011) / 2.04 (1.40-2.99)
(b)
Adults / Children / Adults + Children**Marker * haplotype / Cases / Controls / Haplotype specific P-value; OR (CI) / Cases / Controls / Haplotype specific P-value; OR (CI) / Cases / Controls / Haplotype specific P-value; OR (CI)
1 4 6 7
C A A T / 31 (17.8) / 52 (8.8) / 0.002; 2.25 (1.39-3.64) / 42 (15.4) / 52 (8.8) / 0.0045; 1.90 (1.23-2.93) / 73 (16.4) / 52 (8.8) / 0.00013; 2.04 (1.40-2.99)
C G A C / 24 (13.8) / 93 (15.7) / NS; / 44 (16.2) / 93 (15.7) / NS / 67 (15.1) / 93 (15.7) / NS
C G G T / 82 (47.1) / 314 (53.0) / NS / 124 (45.6) / 314 (53.0) / NS / 205 (47.3) / 314 (46.2) / 0.026; 1.32(1.03-1.68)
T G G C / 37 (21.3) / 133 (22.5) / NS / 62 (22.8) / 133 (22.5) / NS / 99 (22.3) / 133 (22.5) / NS
* 1-rs11238131; 4-rs6592961; 6-rs1982406; 7-rs2044859.
** One child with ADHD was excluded from the clinical sample when adults and infants were analyzed together because he was offspring of an adult ADHD patient.
5000 permutations due to computational limitations.
Down-represented in combined ADHD patients in comparison with controls.
1