This project is to develop and apply strategies for conducting whole genome association (WGA) studies ofmultiple 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 areconducted one phenotype at a time. The Northern Finland Birth Cohort of 1966 (NFBC1966) offers a richphenotype database from a genetically homogeneous population and is therefore ideal for initiation of aphenomic 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 nucleotidepolymorphisms (SNPs), providing excellent power to detect associations to these phenotypes, at agenomewide level of significance, even for genetic variants of relatively modest effect. Genotyping theremaining 3000 members of NFBC1966 using the significant SNPs will permit replication of theseassociations.To implement a phenomic approach, the investigative team will develop and apply methodology thatenables efficient analysis of the phenotype-genotype data. Data mining will identify novel compositephenotypes. A variety of statistical methods will be applied to the problem of analyzing large numbers ofphenotypes. In particular, these methods will use genotype data to determine whether novel phenotypeshave a genetic basis, will analyze the joint contributions of multiple genomic locations'to phenotypicvariation, and will explore the use of genotypic similarity between subjects as a means to genetically maplarge numbers of phenotypes. This methodology will also be used to analyze the WGA data from aCalifornian cohort to be collected by the Consortium for Neuropsyehiatric Phenomics.
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