This project is to develop and apply strategies for conducting whole genome association (WGA) studies of multiple neurobehavioral phenotypes. It is now feasible to conduct well powered WGA studies;however, progress in understanding the biological basis of neuropsyehiatric diseases will be slow if such studies are conducted one phenotype at a time. The Northern Finland Birth Cohort of 1966 (NFBC1966) offers a rich phenotype database from a genetically homogeneous population and is therefore ideal for initiation of a phenomic approach: the joint analysis of whole genome genotypes with an extensive set of phenotypes. Almost 2000 members of NFBC1966 will be genotyped using a densely spaced array of single nucleotide polymorphisms (SNPs), providing excellent power to detect associations to these phenotypes, at a genomewide level of significance, even for genetic variants of relatively modest effect. Genotyping the remaining 3000 members of NFBC1966 using the significant SNPs will permit replication of these associations. To implement a phenomic approach, the investigative team will develop and apply methodology that enables efficient analysis of the phenotype-genotype data. Data mining will identify novel composite phenotypes. A variety of statistical methods will be applied to the problem of analyzing large numbers of phenotypes. In particular, these methods will use genotype data to determine whether novel phenotypes have a genetic basis, will analyze the joint contributions of multiple genomic locations'to phenotypic variation, and will explore the use of genotypic similarity between subjects as a means to genetically map large numbers of phenotypes. This methodology will also be used to analyze the WGA data from a Californian cohort to be collected by the Consortium for Neuropsyehiatric Phenomics.
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