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To investigate the genetic association between gestational duration and fetal mental disorders using Mendelian randomization (MR), and to explore the mediating role of brain functional networks in this pathway through two-step Mendelian randomization (TSMR).
Using gestational duration as the exposure and six mental disorders (autism spectrum disorder[ASD], anorexia nervosa [AN], schizophrenia, etc.) as outcomes, with 191 resting-state functional MRI traits as potential mediators, we analyzed publicly available GWAS summary data. The inverse-variance weighted (IVW) method, MR-Egger regression, and weighted median method were employed to estimate causal effects. TSMR was used to assess the mediating role of brain functional networks, and sensitivity analyses were conducted to evaluate robustness.
Gestational duration showed negative genetic associations with ASD (OR=0.58, 95% CI: 0.48-0.69), AN (OR=0.77, 95% CI: 0.66-0.89), and schizophrenia (OR=0.85, 95% CI: 0.74-0.96). Brain networks, including the salience, central executive, and default mode networks, partially mediated the genetic association between gestational duration and mental disorders, with mediation proportions ranging from 19.09% to 52.40%.
Longer gestational duration reduces the risk of mental disorders, and brain functional networks mediate this genetic association.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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