Background
Methods
Sample population and biosample collection
MARBLES
EARLI
Diagnostic outcomes
Demographic characteristics
RNA isolation and expression assessment
Data preprocessing
Surrogate variable analysis
Differential gene expression
Gene overlap analysis
Overrepresentation enrichment analysis
Gene set enrichment analysis
Weighted gene correlation network analysis
Cell type proportion deconvolution
Results
Study sample characteristics
Child 36 month outcome | ||||
---|---|---|---|---|
ASD (n = 41) | Non-TD (n = 44) | TD (n = 77) | p valuea | |
Child male gender, n (%) | 30 (73.2) | 27 (61.4) | 40 (51.9) | 0.08 |
Child race and ethnicity, n (%) | 0.90 | |||
White (European or Middle Eastern) | 19 (46.3) | 18 (40.9) | 38 (49.4) | |
Black/African-American | 2 (4.9) | 2 (4.5) | 1 (1.3) | |
Asian or Pacific Islander | 4 (9.8) | 3 (6.8) | 7 (9.1) | |
Hispanic White | 8 (19.5) | 11 (25) | 19 (24.7) | |
Hispanic Non-White | 4 (9.8) | 3 (6.8) | 6 (7.8) | |
Multiracial | 4 (9.8) | 7 (15.9) | 6 (7.8) | |
Mother age (years), mean (SD)b | 35.4 (5.1) | 34.1 (4.3) | 33.3 (4.9) | 0.09 |
Father age (years), mean (SD)c | 38.7 (5.3) | 36.1 (4.8) | 35.7 (6.2) |
0.02
k
|
Mother prepregnancy BMI, mean (SD)d | 27.9 (7.4) | 29.3 (8.3) | 26.1 (6.2) | 0.05 |
Mother type 1 diabetes, n (%)e | 0 (0) | 0 (0) | 1 (1.3) | 1.00 |
Mother type 2 diabetes, n (%)e | 0 (0) | 0 (0) | 1 (1.3) | 1.00 |
Mother gestational diabetes, n (%)f | 12 (30) | 6 (14.3) | 11 (14.7) | 0.12 |
Mother hypertension, n (%)e | 1 (2.6) | 1 (2.3) | 1 (1.3) | 1.00 |
Mother preeclampsia, n (%)g | 2 (5.1) | 4 (10) | 2 (2.7) | 0.29 |
Mother smoking by urine cotinine, n (%)h | 4 (17.4) | 1 (4.3) | 1 (2.9) | 0.12 |
Mother bachelor’s degree +, n (%) | 18 (43.9) | 19 (43.2) | 40 (51.9) | 0.57 |
Father bachelor’s degree +, n (%) | 21 (51.2) | 19 (43.2) | 39 (50.6) | 0.69 |
Own home, n (%)i | 21 (55.3) | 25 (58.1) | 48 (63.2) | 0.69 |
Cesarean delivery, n (%)j | 11 (26.8) | 17 (38.6) | 31 (41.3) | 0.28 |
Gestational age (weeks), mean (SD) | 39.4 (1.1) | 39 (1.3) | 38.7 (1.4) |
0.04
k
|
Birth weight (kg), mean (SD) | 3.5 (0.4) | 3.5 (0.4) | 3.4 (0.5) | 0.52 |
Child 36 month outcome | ||||
---|---|---|---|---|
ASD (n = 18) | Non-TD (n = 48) | TD (n = 43) | p valuea | |
Child male gender, n (%) | 13 (72.2) | 23 (47.9) | 19 (44.2) | 0.13 |
Child race and ethnicity, n (%)b |
0.02
h
| |||
White (European or Middle Eastern) | 6 (35.3) | 23 (48.9) | 24 (55.8) | |
Black/African-American | 3 (17.6) | 8 (17) | 1 (2.3) | |
Asian or Pacific Islander | 2 (11.8) | 5 (10.6) | 0 (0) | |
Hispanic White | 2 (11.8) | 3 (6.4) | 3 (7) | |
Hispanic Non-White | 2 (11.8) | 7 (14.9) | 8 (18.6) | |
Multiracial | 2 (11.8) | 1 (2.1) | 7 (16.3) | |
Mother age (years), mean (SD) | 34.4 (4) | 33.8 (4.3) | 34.7 (5) | 0.60 |
Father age (years), mean (SD) | 35.4 (6.8) | 35.7 (5) | 36.2 (6.4) | 0.88 |
Mother prepregnancy BMI, mean (SD)c | 29.4 (7.1) | 27.4 (7) | 27.9 (7.2) | 0.60 |
Mother smoking by urine cotinine, n (%)d | 1 (6.3) | 1 (2.3) | 0 (0) | 0.30 |
Mother bachelor’s degree +, n (%) | 8 (44.4) | 28 (58.3) | 29 (67.4) | 0.26 |
Father bachelor’s degree +, n (%)e | 7 (38.9) | 28 (62.2) | 25 (58.1) | 0.24 |
Own home, n (%) | 8 (44.4) | 31 (64.6) | 36 (83.7) |
0.01
h
|
Cesarean delivery, n (%)f | 9 (56.3) | 17 (39.5) | 12 (35.3) | 0.38 |
Gestational age (weeks), mean (SD) | 39.2 (1.4) | 39.4 (1.5) | 39.1 (1.5) | 0.70 |
Birth weight (kg), mean (SD)g | 3.5 (0.6) | 3.5 (0.6) | 3.5 (0.6) | 1.00 |
ASD-associated differential gene expression in cord blood
Probe ID | Gene symbol | MARBLES | EARLI | Meta-analysis | |||||
---|---|---|---|---|---|---|---|---|---|
log2(FC) | p value | log2(FC) | p value | log2(FC) | SE | p value | q value | ||
17004333 |
TUBB2A
| 0.36 | 9.6E−03 | 0.33 | 2.1E−01 | 0.35 | 0.12 | 4.8E−03 | 0.75 |
17094496 |
MIR1299
| 0.28 | 6.1E−03 | 0.15 | 2.3E−01 | 0.23 | 0.08 | 4.3E−03 | 0.75 |
17065047 |
LOC389831
| 0.26 | 6.1E−03 | 0.16 | 2.4E−01 | 0.23 | 0.08 | 4.2E−03 | 0.74 |
17063807 |
TRBV11-2
| 0.22 | 1.7E−02 | 0.19 | 1.7E−01 | 0.21 | 0.08 | 7.0E−03 | 0.79 |
16812322 |
RNU6-667P
| 0.13 | 1.4E−01 | 0.34 | 4.1E−03 | 0.20 | 0.07 | 3.7E−03 | 0.73 |
16662296 |
RNA5SP42
| 0.22 | 3.1E−03 | 0.12 | 4.4E−01 | 0.20 | 0.07 | 3.0E−03 | 0.73 |
17079513 |
RNU6-748P
| 0.15 | 1.3E−01 | 0.26 | 1.5E−02 | 0.20 | 0.07 | 6.4E−03 | 0.78 |
16837063 |
SNORA76C
| 0.20 | 2.5E−02 | 0.19 | 1.5E−01 | 0.20 | 0.08 | 9.2E−03 | 0.83 |
16755265 |
MIR331
| 0.15 | 2.1E−02 | 0.26 | 7.0E−04 | 0.20 | 0.05 | 6.4E−05 | 0.47 |
16698226 |
LINC01136
| 0.17 | 3.0E−02 | 0.30 | 4.9E−02 | 0.20 | 0.07 | 5.4E−03 | 0.76 |
16738477 |
RP11-872D17.8
| 0.22 | 2.6E−03 | 0.12 | 3.2E−01 | 0.19 | 0.06 | 2.3E−03 | 0.72 |
16797869 |
HERC2P7
| − 0.17 | 4.7E−02 | − 0.22 | 5.4E−02 | − 0.19 | 0.07 | 7.0E−03 | 0.79 |
16778413 |
TPTE2P5
| − 0.25 | 4.9E−04 | − 0.01 | 9.2E−01 | − 0.19 | 0.06 | 2.3E−03 | 0.72 |
16865104 |
MIR519A2
| − 0.28 | 3.5E−05 | − 0.07 | 3.3E−01 | − 0.19 | 0.05 | 1.8E−04 | 0.70 |
17113511 |
RNU6-154P
| − 0.22 | 1.9E−03 | − 0.13 | 2.6E−01 | − 0.20 | 0.06 | 1.4E−03 | 0.72 |
16810171 |
RP11-507B12.1
| − 0.23 | 3.1E−03 | − 0.16 | 1.8E−01 | − 0.21 | 0.07 | 1.6E−03 | 0.72 |
17062251 |
RNA5SP241
| − 0.15 | 5.8E−02 | − 0.45 | 3.4E−03 | − 0.21 | 0.07 | 2.6E−03 | 0.72 |
16788697 |
SNORD114-28
| − 0.29 | 9.1E−03 | − 0.17 | 2.8E−01 | − 0.25 | 0.09 | 6.7E−03 | 0.78 |
16928422 |
CTA-390C10.10
| − 0.17 | 9.8E−02 | − 0.55 | 4.3E−04 | − 0.29 | 0.09 | 7.2E−04 | 0.72 |
16733787 |
RP11-304M2.6
| − 0.28 | 1.5E−02 | − 0.40 | 5.3E−02 | − 0.31 | 0.10 | 2.6E−03 | 0.72 |
Non-TD-associated differential gene expression in cord blood
Probe ID | Gene symbol | MARBLES | EARLI | Meta-analysis | |||||
---|---|---|---|---|---|---|---|---|---|
log2(FC) | p value | log2(FC) | p value | log2(FC) | SE | p value | q value | ||
16761521 |
TAS2R46
| 0.43 | 6.7E−03 | 0.29 | 9.3E−02 | 0.37 | 0.12 | 1.7E−03 | 0.78 |
16846019 |
FAM215A
| 0.08 | 4.5E−01 | 0.32 | 9.5E−04 | 0.22 | 0.07 | 2.5E−03 | 0.85 |
17063807 |
TRBV11-2
| 0.30 | 9.4E−04 | 0.14 | 9.3E−02 | 0.21 | 0.06 | 4.5E−04 | 0.74 |
17094496 |
MIR1299
| 0.17 | 7.7E−02 | 0.22 | 2.1E−02 | 0.20 | 0.07 | 3.8E−03 | 0.91 |
16842217 |
SNORD3D
| 0.13 | 7.0E−02 | 0.25 | 2.9E−03 | 0.18 | 0.05 | 8.3E−04 | 0.74 |
16818580 |
RNA5SP415
| 0.16 | 6.8E−02 | 0.20 | 5.1E−02 | 0.18 | 0.07 | 7.9E−03 | 0.91 |
16846016 |
LRRC37A2
| 0.09 | 3.5E−01 | 0.24 | 6.4E−03 | 0.17 | 0.06 | 7.6E−03 | 0.91 |
16902656 |
RNA5SP103
| 0.22 | 3.0E−03 | 0.06 | 5.2E−01 | 0.16 | 0.06 | 5.5E−03 | 0.91 |
16975969 |
RNU6-310P
| 0.20 | 1.6E−03 | 0.08 | 2.5E−01 | 0.15 | 0.05 | 1.6E−03 | 0.78 |
16845957 |
LRRC37A4P
| 0.21 | 9.3E−03 | 0.11 | 1.1E−01 | 0.15 | 0.05 | 3.8E−03 | 0.91 |
16788576 |
SNORD113-3
| 0.14 | 1.1E−02 | 0.15 | 7.2E−03 | 0.14 | 0.04 | 2.0E−04 | 0.74 |
16840210 |
SLC52A1
| 0.19 | 3.4E−05 | 0.08 | 8.6E−02 | 0.14 | 0.03 | 1.7E−05 | 0.34 |
16774442 |
SMIM2-AS1
| 0.14 | 1.6E−03 | 0.14 | 4.8E−03 | 0.14 | 0.03 | 1.9E−05 | 0.34 |
16985844 |
PMCHL2
| 0.11 | 2.9E−02 | 0.17 | 1.4E−02 | 0.14 | 0.04 | 1.3E−03 | 0.74 |
16805216 |
ASB9P1
| − 0.15 | 1.6E−02 | − 0.13 | 3.6E−02 | − 0.14 | 0.04 | 1.4E−03 | 0.74 |
17078751 |
REXO1L1P
| − 0.14 | 2.3E−03 | − 0.12 | 1.0E−01 | − 0.14 | 0.04 | 5.2E−04 | 0.74 |
16728518 |
FAM86C1
| − 0.21 | 6.6E−03 | − 0.08 | 3.1E−01 | − 0.15 | 0.06 | 7.8E−03 | 0.91 |
17061129 |
RASA4
| − 0.20 | 6.3E−03 | − 0.09 | 2.7E−01 | − 0.16 | 0.06 | 5.0E−03 | 0.91 |
16836858 |
RNU6-446P
| − 0.26 | 3.2E−03 | − 0.06 | 5.7E−01 | − 0.18 | 0.07 | 7.1E−03 | 0.91 |
16733848 |
RP11-326C3.7
| − 0.07 | 4.4E−01 | − 0.33 | 9.6E−04 | − 0.20 | 0.07 | 3.8E−03 | 0.91 |