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A trans-ethnic two-stage polygenetic scoring analysis detects genetic correlation between osteoporosis and schizophrenia

机译：反式民族的两阶段多遗传学分析检测骨质疏松症和精神分裂症之间的遗传相关性

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Backgrounds To explore the genetic correlation between schizophrenia (SCZ) and osteoporosis (OP). Design, setting, participants, measurements We conducted a trans-ethnic two-stage genetic correlation analysis of OP and SCZ, totally invoking 2286 Caucasia subjects in discovery stage and 4124 Chinese subjects in replication stage. The bone mineral density (BMD) and bone area values of ulna & radius, hip and spine were measured using Hologic 4500W dual energy X-ray absorptiometry machine. SCZ was diagnosed according to DSM-IV criteria. For the genome-wide association study (GWAS) of Caucasian OP, Chinese OP and Chinese SCZ, SNP genotyping was performed using Affymetrix SNP 6.0 array. For the GWAS of Caucasian SCZ, SNP genotyping was conducted using the Affymetrix 5.0 array, Affymetrix 6.0 array and Illumina 550 K array. Polygenetic risk scoring (PRS) analysis was conducted by PRSice software. Also, Linkage disequilibrium score regression (LD Score regression) analysis was performed to evaluate the genetic correlation between OP and SCZ. Multi-trait analysis of GWAS (MTAG) was performed to detect novel candidate genes for osteoporosis and SCZ. Results In the Caucasia discovery samples, significant genetic correlations were observed for ulna & radius BMD vs. SCZ (P value = 0.010), ulna & radius area vs. SCZ (P value = 0.031). In the Chinese replication samples, we observed significant correlation for ulna & radius area vs. SCZ (P value = 0.019). In addition, LD Score regression also identified significant genetic correlations between SCZ and bone phenotypes in Caucasian and Chinese sample respectively. MTAG analysis identified several novel candidate genes, such as CTNNA2 (MTAG P value = 2.24 x 10(-6)) for SCZ and FADS2 (MTAG P value = 2.66 x 10(-7)) for osteoporosis. Conclusions Our study results support the overlapped genetic basis for osteoporosis and SCZ, and provide novel clues for elucidating the biological mechanism of increased osteoporosis risk in SCZ patients.
机译：探讨精神分裂症（SCZ）与骨质疏松症（OP）之间的遗传相关性的背景。设计，设定，参与者，测量我们进行了OP和SCZ的反式族两级遗传相关分析，在发现阶段的发现阶段和4124个中华科目中完全调用了2286个白种人科目。使用HOLOLIC 4500W双能X射线吸收机械测量骨密度（BMD）和骨质骨密度，髋部和脊柱的骨密度（BMD）和骨骼区值。 SCZ根据DSM-IV标准诊断出来。对于白种人OP，中国OP和中国SCZ的基因组关联研究（GWA），使用Affymetrix SNP 6.0阵列进行SNP基因分型。对于白种人SCZ的GWA，使用Affymetrix 5.0阵列进行SNP基因分型，Affymetrix 6.0阵列和Illumina 550 K阵列进行。 Prsice软件进行多种危险评分（PRS）分析。此外，进行了联系不平衡评分回归（LD评分回归）分析以评估OP和SCZ之间的遗传相关性。对GWAS（MTAG）进行多种特征分析以检测骨质疏松症和SCZ的新候选基因。结果在Caucasia发现样品中，针对Ulna＆Radius BMD与SCZ（P值= 0.010），ULNA＆RADIUS区域与SCZ（P值= 0.031），观察到显着的遗传相关性。在中文复制样品中，我们观察到尺子和半径区域与SCZ的显着相关性（P值= 0.019）。此外，LD评分回归还分别鉴定了高加索和中华样本中SCZ和骨表型之间的显着遗传相关性。 MTAG分析鉴定了用于SCZ和FADS2（MTAG P值= 2.66×10（-7）的CTNNA2（MTAG P值= 2.24×10（-6））的几种新型候选基因。结论我们的研究结果支持骨质疏松症和SCZ重叠的遗传基础，并提供了阐明SCZ患者骨质疏松症风险增加的生物学机制的新线索。

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