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Is rs7566605, a SNP near INSIG2, associated with body mass in a randomized clinical trial of antipsychotics in schizophrenia?

Molecular Psychiatry volume 12, pages 321–322 (2007)Cite this article

In a recent Science paper, Herbert et al.1 provided compelling data supporting the association of the single nucleotide polymorphism (SNP) rs7566605 with body mass index (BMI) and obesity. rs7566605 was identified in an initial genome-wide association screen and subsequently replicated in five of six samples (meta-analytic odds ratio with obesity 1.22, 95% CI 1.05–1.42, P=0.008 under a recessive model).1 Using baseline and longitudinal data from the CATIE randomized clinical trial of schizophrenia,2 we first investigated whether rs7566605 was associated with BMI and second, given the paucity of genotyping in the region of this SNP in the original report, whether other SNPs in the same haplotype block were associated.

We genotyped rs7566605 (chr2:118,552,255) plus 10 additional SNPs in 756 participants in CATIE, a double-blinded randomized clinical trial of typical and atypical antipsychotics under controlled conditions with follow-up for as long as 18 months, and in which all subjects provided informed consent under IRB approval.2 Briefly, inclusion criteria required a definite diagnosis of schizophrenia, age 18–65 years, clinical decision that oral medication was appropriate, adequate decisional capacity and provision of written informed consent. Exclusion criteria essentially stipulated that participation was safe and clinically reasonable.3 BMI was measured serially across the trial.3 Haplotype tagging SNPs were selected (by applying TAGGER4 to the HapMap2 genotypes for CEU and YRI samples) and genotyped using TaqMan5 blind to all phenotypic data. All SNPs passed quality control (48 duplicate samples/SNP agreed with originals, overall no-call rate was 0.53%, and all SNPs were in Hardy–Weinberg equilibrium). Analyses were conducted using multiple regression in SAS6 and haplotype analyses with haplo.score.7 This is the third CATIE association paper (http://www.med.unc.edu/~pfsulliv/downloads.htm).

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References

  1. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T et al. Science 2006; 312: 279–283.

  2. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO et al. N Engl J Med 2005; 353: 1209–1223.

  3. Stroup TS, McEvoy JP, Swartz MS, Byerly MJ, Glick ID, Canive JM et al. Schizophr Bull 2003; 29: 15–31.

  4. de Bakker PI, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D . Nat Genet 2005; 37: 1217–1223.

  5. Sullivan PF, Keefe RSE, Lange LA, Lange EM, Stroup TS, Lieberman JA et al. Bio Psychiatry (in press).

  6. SAS Institute Inc. SAS/STAT® Software: Version 9. SAS Institute, Inc.: Cary, NC, 2004.

  7. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA . Am J Hum Genet 2002; 70: 425–434.

  8. McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L et al. Schizophr Res 2005; 80: 19–32.

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Authors and Affiliations

  1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    T Skelly, A P Pinheiro, L A Lange & P F Sullivan

  2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    P F Sullivan

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  1. T Skelly
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  2. A P Pinheiro
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  3. L A Lange
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  4. P F Sullivan
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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Skelly, T., Pinheiro, A., Lange, L. et al. Is rs7566605, a SNP near INSIG2, associated with body mass in a randomized clinical trial of antipsychotics in schizophrenia?. Mol Psychiatry 12, 321–322 (2007). https://doi.org/10.1038/sj.mp.4001956

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