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Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples.

Publication ,  Journal Article
Talkowski, ME; McClain, L; Allen, T; Bradford, LD; Calkins, M; Edwards, N; Georgieva, L; Go, R; Gur, R; Gur, R; Kirov, G; Chowdari, K ...
Published in: Am J Med Genet B Neuropsychiatr Genet
June 5, 2009

Recessive mutations in the phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Previous studies have suggested PAH variations could confer risk for schizophrenia, but comprehensive follow-up has not been reported. We analyzed 15 common PAH "tag" SNPs and three exonic variations that are rare in Caucasians but common in African-Americans among four independent samples (total n = 5,414). The samples included two US Caucasian cohorts (260 trios, 230 independent cases, 474 controls), Bulgarian families (659 trios), and an African-American sample (464 families, 401 controls). Analyses of both US Caucasian samples revealed associations with five SNPs; most notably the common allele (G) of rs1522305 from case-control analyses (z = 2.99, P = 0.006). This SNP was independently replicated in the Bulgarian cohort (z = 2.39, P = 0.015). A non-significant trend was also observed among African-American families (z = 1.39, P = 0.165), and combined analyses of all four samples were significant (rs1522305: chi(2) = 23.28, 8 d.f., P = 0.003). Results for rs1522305 met our a priori criteria for statistical significance, namely an association that was robust to multiple testing correction in one sample, a replicated risk allele in multiple samples, and combined analyses that were nominally significant. Case-control results in African-Americans detected an association with L321L (P = 0.047, OR = 1.46). Our analyses suggest several associations at PAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted.

Duke Scholars

Published In

Am J Med Genet B Neuropsychiatr Genet

DOI

EISSN

1552-485X

Publication Date

June 5, 2009

Volume

150B

Issue

4

Start / End Page

560 / 569

Location

United States

Related Subject Headings

  • Schizophrenia
  • Polymorphism, Single Nucleotide
  • Phenylketonurias
  • Phenylalanine Hydroxylase
  • Mutation
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
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Talkowski, M. E., McClain, L., Allen, T., Bradford, L. D., Calkins, M., Edwards, N., … Nimgaonkar, V. L. (2009). Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. Am J Med Genet B Neuropsychiatr Genet, 150B(4), 560–569. https://doi.org/10.1002/ajmg.b.30862
Talkowski, Michael E., Lora McClain, Trina Allen, L Dianne Bradford, Monica Calkins, Neil Edwards, Lyudmila Georgieva, et al. “Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples.Am J Med Genet B Neuropsychiatr Genet 150B, no. 4 (June 5, 2009): 560–69. https://doi.org/10.1002/ajmg.b.30862.
Talkowski ME, McClain L, Allen T, Bradford LD, Calkins M, Edwards N, et al. Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):560–9.
Talkowski, Michael E., et al. “Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples.Am J Med Genet B Neuropsychiatr Genet, vol. 150B, no. 4, June 2009, pp. 560–69. Pubmed, doi:10.1002/ajmg.b.30862.
Talkowski ME, McClain L, Allen T, Bradford LD, Calkins M, Edwards N, Georgieva L, Go R, Gur R, Kirov G, Chowdari K, Kwentus J, Lyons P, Mansour H, McEvoy J, O’Donovan MC, O’Jile J, Owen MJ, Santos A, Savage R, Toncheva D, Vockley G, Wood J, Devlin B, Nimgaonkar VL. Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):560–569.
Journal cover image

Published In

Am J Med Genet B Neuropsychiatr Genet

DOI

EISSN

1552-485X

Publication Date

June 5, 2009

Volume

150B

Issue

4

Start / End Page

560 / 569

Location

United States

Related Subject Headings

  • Schizophrenia
  • Polymorphism, Single Nucleotide
  • Phenylketonurias
  • Phenylalanine Hydroxylase
  • Mutation
  • Male
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetic Predisposition to Disease