Lee Byung Dae, Gonzalez Suzanne, Villa Erika, Camarillo Cynthia, Rodriguez Marco, Yao Yin, Guo Wei, Flores Deborah, Jerez Alvaro, Raventos Henriette, Ontiveros Alfonso, Nicolini Humberto, Escamilla Michael
Center of Excellence for Neurosciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas.
Department of Psychiatry, School of Medicine, Pusan National University, Busan, South Korea.
Am J Med Genet B Neuropsychiatr Genet. 2017 Oct;174(7):683-690. doi: 10.1002/ajmg.b.32551. Epub 2017 May 29.
Personality traits have been suggested as potential endophenotypes for Bipolar Disorder (BP), as they can be quantitatively measured and show correlations with BP. The present study utilized data from 2,745 individuals from 686 extended pedigrees originally ascertained for having multiplex cases of BP (963 cases of BPI or schizoaffective BP). Subjects were assessed with the NEO Personality Inventory, Revised (NEO PI-R) and genotyped using the Illumina HumanLinkage-24 Bead Chip, with an average genetic coverage of 0.67 cM. Two point linkage scores were calculated for each trait as a quantitative variable using SOLAR (Sequential Oligogenic Linkage Analysis Routines). Suggestive evidence for linkage was found for neuroticism at 1q32.1 (LOD = 2.52), 6q23.3 (2.32), 16p12 (2.79), extraversion at 4p15.3 (2.33), agreeableness at 4q31.1 (2.37), 5q34 (2.80), 7q31.1 (2.56), 16q22 (2.52), and conscientiousness at 4q31.1 (2.50). Each of the above traits have been shown to be correlated with the broad BP phenotype in this same sample. In addition, for the trait of openness, we found significant evidence of linkage to chromosome 3p24.3 (rs336610, LOD = 4.75) and suggestive evidence at 1q43 (2.74), 5q35.1 (3.03), 11q14.3 (2.61), 11q21 (2.30), and 19q13.1 (2.52). These findings support previous linkage findings of the openness trait to chromosome 19q13 and the agreeableness trait to 4q31 and identify a number of new loci for personality endophenotypes related to bipolar disorder.
人格特质已被认为是双相情感障碍(BP)潜在的内表型,因为它们可以进行定量测量并与双相情感障碍相关。本研究使用了来自686个扩展家系的2745名个体的数据,这些家系最初是因有多例双相情感障碍(963例双相I型或分裂情感性双相障碍)而确定的。受试者使用修订版的大五人格量表(NEO PI-R)进行评估,并使用Illumina HumanLinkage-24 Bead芯片进行基因分型,平均遗传覆盖率为0.67 cM。使用SOLAR(顺序寡基因连锁分析程序)将每个特质作为定量变量计算两点连锁分数。在1q32.1(LOD = 2.52)、6q23.3(2.32)、16p12(2.79)发现了与神经质相关的连锁的提示性证据,在4p15.3(2.33)发现了与外向性相关的连锁的提示性证据,在4q31.1(2.37)、5q34(2.80)、7q31.1(2.56)、16q22(2.52)发现了与宜人性相关的连锁的提示性证据,在4q31.1(2.50)发现了与尽责性相关的连锁的提示性证据。在同一样本中,上述每个特质均已显示与广泛的双相情感障碍表型相关。此外,对于开放性特质,我们发现与3p24.3染色体(rs336610,LOD = 4.75)存在显著连锁证据,在1q43(2.74)、5q35.1(3.03)、11q14.3(2.61)、11q21(2.30)和19q13.1(2.52)发现了提示性证据。这些发现支持了先前关于开放性特质与19q13染色体以及宜人性特质与4q31染色体的连锁发现,并确定了一些与双相情感障碍相关的人格内表型的新基因座。