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Next-Generation Sequencing in Genetic Studies of Psychiatric Disorders 

Next-Generation Sequencing in Genetic Studies of Psychiatric Disorders
Next-Generation Sequencing in Genetic Studies of Psychiatric Disorders

Shweta Ramdas

and Jun Z. Li

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date: 17 May 2022

Next-generation sequencing (NGS) technologies make it possible to efficiently detect DNA variants in either entire genomes or any subsets of the genome, and have dramatically enhanced our ability to search for genetic risk factors of complex psychiatric diseases. While genotyping-based association studies focus on common variants that track extended genomic segments, NGS provides unbiased identification of both common and rare variants, including those that are functionally important but appear in very few families or sporadic cases. Thus NGS directly highlights plausible causal variants, even if such variants are extremely heterogeneous in the population. Meanwhile, such heterogeneity requires new analytical approaches that can aggregate rare variant burden over predefined functional unit such as a gene or a segment of non-coding region with presumed function. Rapid application of NGS technologies also underscored other limits in psychiatric genetics research, including the need for detailed phenotyping and multi-scale integration of diverse data types.

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