儿童青少年脑容积比内表型的双生子研究

Endophenotype of brain volume ratio in children and adolescents: a twin study

目的探索儿童青少年脑灰白质容积比、灰质全脑容积比、白质全脑容积比是否为稳定内表型，作为儿童脑发育的关键内表型指标。方法采用横断面设计双生子法，以学籍登记为线索募集12～18岁的双生子，采集静脉血液标本提取DNA，进行卵型鉴定。采用中国修订版-韦氏儿童智力量表进行智商测定。用3.0T MRI（GE）对双生子对进行头颅结构扫描，采集全脑166层矢状位图像。结果①最终符合条件58对双生子成功提取DNA，卵型鉴定结果显示：同卵双生子31对，异卵双生子27对；②灰质容积、白质容积、脑脊液容积、全脑容积、灰白质容积比、灰质全脑容积比、白质全脑容积比在MZ间均呈正相关（P〈0.01）；DZ除灰质全脑容积比及脑脊液容积呈正相关（P〈0.05）外，其余5项差异无统计学意义（P〉0.05）；Holzinger方法估计灰白质容积比遗传度0.828，灰质全脑容积比遗传度为0.596，白质全脑容积比遗传度为0.741。结论为克服个体脑容积差异而候选的3个容积比中，无脑脊液容积影响的灰白质容积比有较高遗传度，说明灰白质容积比有相对稳定的遗传基础，可以作为儿童青少年脑发育的内表型指标。

Objective To explore whether brain volume ratios such as gray-to-white matter volume ratio, gray matter-to-global volume ratio, and white matter-to-global volume ratio are stable endophenotypes which can be used as key endophenotype indexes of children and adolescents’ brain development. Methods Using cross-sectional design, totally 58 pairs of twins aged 12 to 18 years were recruited according to the school registration information. DNA was extracted from venous blood samples to identify zygosity. Intelligence quotients （IQ） of participants were measured with C-Wechsler intelligence scale for children （C-WISC）. With 3.0T MRI （GE）, we examined all 58 twin pairs to obtain brain structure MR image for each person. Results （1） The 58 twin pairs included 31 monozygotic twin pairs （MZ group） and 27 dizygotic twin pairs （DZ group）. （2） Gray matter volume, white matter volume, cerebrospinal fluid volume, global cerebral volume, gray-to-white matter volume ratio, gray matter-to-global volume ratio and white matter-to-global volume ratio were positively associated （P〈0.01） in the MZ group. Cerebrospinal fluid volume and gray matter-to-global volume ratio showed positive correlation （P〈0.05） in the DZ group while other 5 indexes showed non-significant difference （P〉0.05）. Heritabilities estimated by Holzinger’s method of gray-to-white matter volume ratio, gray matter-to-global volume ratio, and white matter-to-global volume ratio were 0.828, 0.596, and 0.741, respectively. Conclusion The heritability of gray-to-white matter volume ratio is highest in all volume ratios and is not affected by cerebrospinal fluid volume. Thus, gray-to-white matter volume ratio may be used as a stable endophenotype indicator for brain development research of children and adolescents.