Biology subjects

Ogishima, S.

Publications and source records attributed to Ogishima, S..

3 recordsLinked to original sources

bioRxiv2019

Clustering by phenotype and genome-wide association study in autism

BackgroundAutism spectrum disorder (ASD) has phenotypically and genetically heterogeneous characteristics. A simulation study demonstrated that attempts to categorize patients with a complex disease into more homogeneous subgroups could have more power to elucidate hidden heritability. MethodsWe conducted cluster analyses using the k-means algorithm with a cluster number of 15 based on phenotypic variables from the Simons Simplex Collection (SSC). As a preliminary study, we conducted a conventional genome-wide association study (GWAS) with a dataset of 597 ASD cases and 370 controls. In the second step, we divided cases based on the clustering results and conducted GWAS in each of the subgroups vs controls (cluster-based GWAS). We also conducted cluster-based GWAS on another SSC dataset of 712 probands and 354 controls in the replication stage. ResultsIn the preliminary study, we observed no significant associations. In the second step of cluster-based GWASs, we identified 65 chromosomal loci, which included 30 intragenic loci located in 21 genes and 35 intergenic loci that satisfied the threshold of P<5.0x10-8. Some of these loci were located within or near previously reported candidate genes for ASD: CDH5, CNTN5, CNTNAP5, DNAH17, DPP10, DSCAM, FOXK1, GABBR2, GRIN2A5, ITPR1, NTM, SDK1, SNCA and SRRM4. Of these 65 significant chromosomal loci, rs11064685 located within the SRRM4 gene had a significantly different distribution in the cases vs. controls in the replication cohort. ConclusionsThese findings suggest that clustering may successfully identify subgroups with relatively homogeneous disease etiologies. Further cluster validation and replication studies are warranted in larger cohorts.

neuroscience↗

bioRxiv2019

GWAS identifies nine nephrolithiasis susceptibility loci related with metabolic and crystallization pathways

Nephrolithiasis is a common urological trait disorder with acute pain. Although previous studies have identified various genetic variations associated with nephrolithiasis, the host genetic factors remain largely unidentified. To identify novel nephrolithiasis loci in the Japanese population, we performed large-scale GWAS (Genome wide association study) using 11,130 cases and 187,639 controls, followed by a replication analysis using 2,289 cases and 3,817 controls. The analysis identified 14 significant loci, including 9 novel loci on 2p23.2-3, 6p21.2, 6p12.3, 6q23.2, 16p12.3, 16q12.2, 17q23.2, 19p13.12, and 20q13.2. Interestingly, 10 of the 14 regions showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic background among nephrolithiasis patients and these quantitative traits. Four novel loci are related to the metabolic pathway, while the remaining 10 loci are associated with the crystallization pathway. Our findings demonstrate the crucial roles of genetic variations in the development of nephrolithiasis.\n\nSIGNIFICANCE STATEMENTNephrolithiasis is a common urothelial disorders with frequent recurrence rate, but its genetic background is largely remained unidentified. Previous GWAS identified 6 genetic factors in total. Here we performed a GWAS using more than 200,000 samples in the Japanese populations, and identified 14 significant loci and nine of them are novel. We also found that 10 of the 14 loci showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (BMI, eGFR, UA, Ca etc). All 14 significant loci are associate with either metabolic or crystallization pathways. Thus, our findings elucidated the underlying molecular pathogenesis of nephrolithiasis.

genetics↗

bioRxiv2019

Management of family relationship informationfor a three-generation cohort study

A system for inputting and storing family information, named \"BirThree Enrollment,\" was developed to promote a birth and three-generation cohort study (BirThree Cohort Study), and this system was operated successfully. In the study, it was necessary to satisfy many operational demands. Input information is overwritten and changed continuously. Complex kinship information must be quickly and accurately input and corrected, and information on those families not yet recruited must be retrieved. For these purposes, many devices are needed, from an input interface to the internal data structure. In the field of genetic statistics, a simple standard expressive form is used for describing family structure. This form has sufficient information for genetics; however, we developed this form further for our purposes in conducting the BirThree Cohort Study. To provide information about family roles as required in the BirThree Cohort Study, we expanded the data structure, and constructed the system that is able to be used for the daily operation. In our system, family pedigree information is stored along with initial clinical information, and enabled the input of all self-reported information to the data base. Operators are able to input this family information before the day is out. As a result, when recruitment is completed, family information will be completed concurrently. Therefore, it is possible to immediately know a certain persons family structure. By using our system, data correction was improved dramatically, and the system was operated successfully. This study is the first report of the method for storing three generations of family data.

epidemiology↗