A Matrilineal Genetic Legacy from the Last Glacial Maximum Confers Susceptibility to Schizophrenia in Han Chinese

Wen Zhang; Jinsong Tang; A-Mei Zhang; Min-Sheng Peng; Hai-Bing Xie; Liwen Tan; Lin Xu; Ya-Ping Zhang; Xiaogang Chen; Yong-Gang Yao

doi:10.1016/j.jgg.2014.05.004

Volume 41 Issue 7

Jul. 2014

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Article Navigation > Journal of Genetics and Genomics > 2014 > 41(7): 397-407

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A Matrilineal Genetic Legacy from the Last Glacial Maximum Confers Susceptibility to Schizophrenia in Han Chinese

doi: 10.1016/j.jgg.2014.05.004

a
Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
b
The Institute of Mental Health, the Second Xiangya Hospital, Central South University, Changsha 410011, China
c
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
d
National Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha 410011, China

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Corresponding author: E-mail address: chenxghn@gmail.com (Xiaogang Chen); E-mail address: yaoyg@mail.kiz.ac.cn (Yong-Gang Yao)
Received Date: 2014-02-28
Accepted Date: 2014-05-21
Rev Recd Date: 2014-05-16

Available Online: 2014-06-02

Publish Date: 2014-07-20

Abstract

Abstract

Mitochondrial dysfunction has been widely reported in schizophrenia patients. To dissect the matrilineal structure of Han Chinese with or without schizophrenia and to decipher the maternal influence and evolutionary history of schizophrenia, a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of Han Chinese origin, were recruited in Hunan Province, China. We classified haplogroup for each individual based on mitochondrial DNA (mtDNA) sequence variations and compared the haplogroup distribution pattern between cases and controls. Haplogroup B5a presented a higher frequency in cases than in controls (P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]), and this result could be confirmed by permutation analysis. Age estimation of haplogroup B5a in cases revealed a much younger age than that of controls, which was coincident with the Northern Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of complete mtDNA in five patients belonging to haplogroup B5a showed that this background effect might be caused by haplogroup-defining variants m.8584G>A and m.10398A>G. Our results showed that matrilineal risk factor for schizophrenia had an ancient origin and might acquire a predisposing effect on schizophrenia due to the environment change and/or orchestration with other nuclear genetic factors appeared recently in human evolutionary history.
- mtDNA haplogroup,
- Schizophrenia,
- Association,
- Last Glacial Maximum,
- Evolutionary medicine

These authors contributed equally to this work.

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References(66)

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