Polygenic Risk Scores and Schizophrenia: Association with Gender and Age of Onset in an Ashkenazi Jewish Population Open Access

Fevrier, Helene Bernadette (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/k643b1453?locale=en


Schizophrenia (SZ) is a severe and debilitating psychiatric disorder with a range of symptoms and outcomes that range from remission to chronic states where treatment options are not effective. Remission in SZ is association with female gender, later age of onset, and good social functioning prior to onset. Twin studies have shown 80% heritability between twins and 60% heritability in family studies. SZ is a polygenic disorder, where the individual contribution of each SNP is minimal, and the pooled effect of many mutations contributes to a higher risk of SZ and other psychiatric disorders, including bipolar disorder (BP). The data for this study was from the Epidemiology Genetics Program at the Johns Hopkins University School of Medicine, where SZ cases and unaffected controls of Ashkenazi Jewish descent were ascertained. Genome-wide SNP data for 600 SZ cases, 446 BP cases, and 508 controls was used to create risk scores for each individual at 3 different association thresholds. Risk scores were investigated for associations between gender and age of onset. Risk score was associated with SZ phenotype after adjusting for sex (OR: 1.20, 1.03-1.40). In females, higher scores may be related to earlier ages of onset; no such relationship was found in men. Risk scores for BP cases were created using a dataset of SZ cases and controls to test whether polygenic risk score, but not gender, was associated with BP phenotype (p<0.0001). Age of onset in BP cases was not associated with risk score. These findings support previous literature that gender is associated with genetic risk for SZ, and that SZ and BP may share common risk alleles.

Table of Contents

I. Introduction ...........1

II. Methods ..............10

III. Results ...............14

IV. Discussion ..........17

V. References............23

VI. Appendix A: .......27

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