Is there an association between NPY and neuroticism?/Zhou et al. reply

• Published in: Nature (London) 2009-04, Vol.458 (7238), p.E6
• Main Authors: Cotton, Colleen H, Flint, Jonathan, Campbell, Thomas G, Zhou, Zhifeng, Zhu, Guanshan, Hariri, Ahmad R, Enoch, Mary-Anne, Scott, David, Sinha, Rajita, Virkkunen, Matti, Mash, Deborah C, Lipsky, Robert H, Hu, Xian-Zhang, Hodgkinson, Colin A, Xu, Ke, Buzas, Beata, Yuan, Qiaoping, Shen, Pei-Hong, Ferrell, Robert E, Manuck, Stephen B, Brown, Sarah M, Hauger, Richard L, Stohler, Christian S, Zubieta, Jon-Kar, Goldman, David
• Format: Article
• Language: English
• Subjects: Behavior; Brain; Dentistry; Environmental conditions; Environmental stress; Gene mapping; Genetics; Measurement errors; Radiology; Regression analysis; Risk factors; Studies
• ISSN: 0028-0836; 1476-4687

To test their claims we genotyped all seven single nucleotide polymorphisms (SNPs) investigated by Zhou et al.1 in 582 singletons from the extreme 5% tails of the Eysenck Personality Questionnaire neuroticism score distribution from a non-clinical population of 88,142 individuals from the south-west of England2. At the extremes of the distribution various confounds such as severe environmental stresses, rare functional alleles and measurement errors are more likely to be over-represented.\n Brain imaging studies have also shown that a functional missense variant (Val158Met) of COMT alters brain activity during cognition7, pain8 and response to emotional stimuli (accounting for 38% of the variance in emotionality9), while having much more modest effects on complex behaviours, including anxiety. Zhifeng Zhou1, Guanshan Zhu1,, Ahmad R. Hariri2, Mary-Anne Enoch1, David Scott3, Rajita Sinha4, Matti Virkkunen5, Deborah C. Mash6, Robert H. Lipsky1, Xian-Zhang Hu1, Colin A. Hodgkinson1, Ke Xu1, Beata Buzas1, Qiaoping Yuan1, Pei-Hong Shen1, Robert E. Ferrell2, Stephen B. Manuck2, Sarah M. Brown2, Richard L. Hauger7, Christian S. Stohler8, Jon-Kar Zubieta3 & David Goldman1 1 Laboratory of Neurogenetics, NIAAA, NIH, Bethesda, Maryland 20892, USA. e-mail: [e-mail] 2 Departments of Psychiatry, Human Genetics, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. 3 Departments of Psychiatry and Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. 4 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA. 5 Department of Psychiatry, University of Helsinki, Helsinki 00014, Finland. 6 Department of Neurology, University of Miami School of Medicine, Miami, Florida 33124, USA. 7 Department of Psychiatry, San Diego VA Healthcare System and University of California, San Diego, California 92161, USA. 8 School of Dentistry, University of Maryland, Baltimore, Maryland 21201, USA. [dagger] Present address: Sirota, L. A., Greenberg, B. D., Murphy, D. L. & Hamer, D. H. Non-linear association between the serotonin transporter promoter polymorphism and neuroticism: a caution against using extreme samples to identify quantitative trait loci.