To Investigate The Association Between Schizophrenia Susceptibility Gene ZNF804A Rs1344706 And Brain Structure And Neural Activity In Healthy Chinese Population

Objiective:By analyzing the differences in brain structure(including cortical thickness,subcortical gray matter and white matter volume,white matter microstructure)and neural activity(ALFF,Re Ho)among different genotypes of rs1344706 single nucleotide polymorphic sites in healthy Chinese population,the possible causes of susceptibility to schizophrenia were further investigated.Methods:A total of 299 healthy Chinese subjects were genotyped for rs1344706 by SNa Pshot method.According to the genotyping results,the subjects were divided into two groups: TT+TG group with effect allele(T)and GG group without effect allele(T).3D-T1 WI images,DTI images and rs-f MRI images were collected and post-processed.Independent sample t test was used to compare the cortical thickness,subcortical gray matter and white matter volume,white matter microstructure and neural activity between the two groups.Results:According to statistical analysis,the differences in age(t test,P=0.234 >0.05),gender and education level(χ~2test,P > 0.05)between the two groups were excluded.In the healthy Chinese population,there was no significant difference in cortical thickness and subcortical gray matter volume between the "TT+TG group" carrying the effect allele of ZNF804 A rs1344706 and the "GG group" without the effect allele(P > 0.05).In subcortical white matter volume,the volumes of the anterior,anterior middle and posterior parts of the corpus callosum of the effect alleles were larger than those of the non-effect alleles,the volumes of the anterior(P=0.014,P < 0.05),anterior middle(P=0.003,P < 0.05)and posterior parts(P=0.027,P < 0.05)of the corpus callosum were statistically significant.There were no significant differences in FA,LDH,AD,RD,and MD values of white matter in the total sample between the two groups based on voxel and atlas level analysis(P >0.05).There were significant differences in the FA,LDH,AD and MD values of some white matter fiber tracts between the two groups(P < 0.05):(1)The FA values of the left superior cerebellar crus and the right superior frontooccipital tract in the effect allele group were lower than those in the non-effect allele group.(2)The LDH values of effector alleles in the right corticospinal tract,right tapetum,left superior cerebellar peduncle,left anterior limb of internal capsule,left posterior corona radiata and left superior frontooccipital tract were higher than those of non-effector alleles.(3)AD values of the left uncinate fasciculus and bilateral tapetum of effector alleles were higher than those of non-effector alleles.(4)The MD value of the left fornix of effector alleles was greater than that of non-effector alleles.(5)There was no significant difference in RD value between the two groups.In the neural activity analysis,the ALFF of the effect allele(P=0.001,corrected by GRF: voxel level P < 0.001,cluster level P < 0.05)was increased in the left lingual gyrus,hippocampus,middle occipital gyrus,inferior parietal angular gyrus,paracentral lobule,right cuneus and superior occipital gyrus,and decreased in the left angular gyrus compared with the non-effect allele.The Re Ho of the effect allele(P < 0.005,corrected by GRF)was lower than that of the non-effect allele in the right middle temporal gyrus(P=0.003),the Re Ho of the right pars triangularis of the inferior frontal gyrus was lower(P=0.005),and the Re Ho of the right superior occipital gyrus was higher(P=0.005).Conclusions:(1)There is insufficient evidence to suggest that ZNF804 A rs1344706single nucleotide polymorphic sites contribute to schizophrenia susceptibility by affecting gray matter structure in healthy Chinese population.(2)The single nucleotide polymorphic sites of ZNF804 A rs1344706 may affect the integrity of the white matter by affecting the white matter structure(white matter volume and white matter microstructure),and lead to the abnormal structural connections in the brain,thus leading to the susceptibility to schizophrenia.(3)ZNF804A rs1344706 single nucleotide polymorphic sites may contribute to susceptibility to schizophrenia by influencing neural activity.