Table 3.
Linkage peaks with support from independent studies*
| Locus | Endpoint | Statistics | Cohort (subsetting) | Best marker |
Candidate genes | Refs |
|---|---|---|---|---|---|---|
| 1q21– 1q23 |
Asperger diagnosis | Zmax = 3.6 (p = 0.0002) | 30 extended families of Finnish origin | D1S484 | – | 150 |
| ASD diagnosis | MLS = 2.6 (p = 0.002) | 38 extended families (strict autism in 21) | D1S1653 | – | 138 | |
| 2q24– 2q31 |
ASD diagnosis | MLS = 4.8 (p = 2 × 10−5) | 152 IMGSAC families (strict autism in 127) | D2S2188 | CENTG2 | 112 |
| ASD diagnosis | NPL = 3.3 (p = 0.0005) | 100 families (speech delay in 49) | D2S364 | – | 57 | |
| 3q25– 3q27 |
ASD diagnosis | MLS = 4.8 (p = 2 × 10−5) | 38 extended families | D3S3037 | – | 138 |
| ASD diagnosis | NPL = 3.5 (p = 0.0003) | Large Utah pedigree with 7 affected children | rs1402229 | – | 139 | |
| 5p13– 5p14 |
ASD diagnosis | Z = 3.4 (p = 0.0003) | 1181 AGP families (194 FC families with ≥2 children with strictly defined autism) |
rs1968011 | – | 5 |
| ASD diagnosis | MLS = 2.5 (p = 0.003) | 110 AGRE families | D5S2494 | – | 140 | |
| ASD diagnosis | MLS = 2.5 (p = 0.003) | 345 AGRE families | D5S1473 | – | 135 | |
| 7q22– 7q31 |
ASD diagnosis | MLS = 3.2 (p = 0.0006) | 152 IMGSAC families | D7S477 |
RELN, MET, CADPS2 |
70,112,117- 121,123 |
| ASD diagnosis | MLS = 3.1 (p = 0.0008) | 170 IMGSAC families | D7S477 | – | 45,111 | |
| 7q34– 7q36 |
Age at first word | Zmax = 3.0 (p = 0.001) | 152 AGRE families | D7S1824 to D7S3058 |
CNTNAP2, EN2 |
14,39,40,129, 130,151,152 |
| Age at first word | Zmax = 2.1 (p = 0.02) | 291 AGRE families (including the 152 from above) |
D7S2426 | – | 68 | |
| 9q33– 9q34 |
Age at first word | Z = 3.5 (p = 0.0002) | 222 CPEA families | D9S164 | – | 15 |
| ASD diagnosis | Z = 3.3 (p = 0.0005) | 1181 AGP families (741 male only) | rs536861 | – | 5 | |
| 11p12– 11p13 |
ASD diagnosis | Z = 4.0 (p = 3 × 10−5) | 1181 AGP families (335 FC; batch CNV‡) | rs1358054 | – | 5 |
| Social responsiveness score |
Zmax = 3.2 (p = 0.0007) | 99 AGRE families | ATA34E08 | – | 69 | |
| 17q11– 17q21 |
ASD diagnosis | MLS = 4.3 (p = 5 × 10−5) | 257 AGRE families (148 male only) | D17S1294 |
ITGB3, SLC6A4 |
54,131-133, 136,137 |
| ASD diagnosis | MLS = 4.1 (p = 8 × 10−5) | 91 AGRE families (48 male only) | D17S2180 | – | 51 | |
| ASD diagnosis | MLS = 2.8 (p = 0.002) | 345 AGRE families | D17S1800 | – | 135 |
An attempt has been made to include all linkage peaks for which at least one study obtained a log10 of odds (LOD) score > 3.0 and a second obtained a LOD > 2.0. LOD is a measure of significance given by the logarithm of the odds under the null (no linkage) and alternative (linkage present) hypotheses. P values for Z scores were obtained in R using the formula pnorm(-abs(Z)); pnorm refers to normal distribution with a mean of 0 and a standard deviation of 1 and abs refers to absolute value. Values for LOD scores were obtained in R using the formula 1/10^(LOD).
Batch CNV refers to the analytic method that was used to identify and remove families with copy number variation (CNV). The candidate genes in the table are: CADPS2, Ca2+-dependent activator protein for secretion 2; CENTG2, centaurin gamma 2; CNTNAP2, contactin associated protein-like 2; EN2, engrailed homeobox 2; ITGB3, integrin beta 3; MET, met proto-oncogene; RELN, reelin; SLC6A4, solute carrier family 6 (neurotransmitter transporter, serotonin) member 4. Other abbreviations: AGP, Autism Genome Project; AGRE, Autism Genetic Resource Exchange; ASD, autism spectrum disorder; CPEA, Collaborative Programs of Excellence in Autism Network at the National Institutes of Health; FC, female containing; IMGSAC, International Molecular Genetic Study of Autism Consortium; MLS, multipoint LOD score; NPL, nonparametric LOD score.