Editorial comment Suggestive evidence on the genetic link between mitochondria dysfunction and autism An editorial comment to Marui T, Funatogawa I, Koishi S et al. ‘‘The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism’’ (1) Among the psychiatric disorders with a strong genetic component, autism is at the top of the list. Genetics accounts for 90% of the vulnerability for Autism. As for any complex trait, a number of genetic variants either from one or several genes contribute to the disease each with a small size effect. Thus, no one single gene will explain all of the susceptibility to Autism. In this issue of the Acta Psychiatrica Scandinativa, Marui et al. (1) reported association of genetic variants known as single-nucleotide polymorphism (SNP) in a mitochondrial gene the NADH-ubiquinone oxidoreductase 1 a subcomplex 5 (NDUFA5) with Autism. They conducted the study in two independent samples, a case–control and a replication sample of families mainly to account for the small sample size of the first cohort. Individual SNP analyses showed association with two SNPs in the case–control study but not in the family sample. When these two SNPs were combined in haplotypes, the A allele for SNP rs12666974 and the T allele for SNP rs3779262 are less frequently present among patients and not transmitted to the affected chil- dren in the family sample. The authors did not report the Odds ratio or the size effect of this genetic contribution that most likely are low. Although mitochondrial dysfunction has been reported in autism spectrum (8%) (2), it is not clear whether this dysfunction contributes directly or indirectly to the susceptibility of Autism. Similarly, this association study is the first to establish a relationship between a mitochondrial gene and Autism. This study is based on a candidate gene for Autism and conducted in two independent samples, a conventional approach in molecular genetics. Whether the results that emerge from this study are false positive may depend on future studies. As the authors indicated in the manuscript, future studies will be necessary to further understand or confirm the role of NDUFA5 in Autism. These studies may include larger sample sizes, presence of mitochondrial dysfunction, and different ethnic background. Ultimately, the valid- ity of any genetic finding relies on biological interpretation and experimental evidence. Sandra Villafuerte Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA E-mail: [email protected] References 1. Marui T, Funatogawa I, Koishi S et al. The NADH-ubiquinone oxidoreductase 1 alpha subcomplex 5 (NDUFA5) gene variants are associated with autism. Acta Psychiatr Scand 2011;123:118–124. 2. Hass R. Autism and mitochondrial disease. Dev Disabil Res Rev 2010;16:144–153. Acta Psychiatr Scand 2011: 123: 95 All rights reserved DOI: 10.1111/j.1600-0447.2010.01654.x Ó 2011 John Wiley & Sons A/S ACTA PSYCHIATRICA SCANDINAVICA 95

Suggestive evidence on the genetic link between mitochondria dysfunction and autism

Download PDF Report

Upload
sandra-villafuerte
View
212
Download
0

Embed Size (px)

Citation preview

Page 1: Suggestive evidence on the genetic link between mitochondria dysfunction and autism

Editorial comment

Suggestive evidence on the genetic linkbetween mitochondria dysfunction andautismAn editorial comment to Marui T, Funatogawa I, Koishi S et al. ‘‘The NADH-ubiquinone oxidoreductase 1

alpha subcomplex 5 (NDUFA5) gene variants are associated with autism’’ (1)

Among the psychiatric disorders with a stronggenetic component, autism is at the top of the list.Genetics accounts for 90% of the vulnerability forAutism. As for any complex trait, a number ofgenetic variants either from one or several genescontribute to the disease each with a small sizeeffect. Thus, no one single gene will explain all ofthe susceptibility to Autism. In this issue of theActa Psychiatrica Scandinativa, Marui et al. (1)reported association of genetic variants known assingle-nucleotide polymorphism (SNP) in a mito-chondrial gene the NADH-ubiquinone oxidore-ductase 1 a subcomplex 5 (NDUFA5) with Autism.They conducted the study in two independentsamples, a case–control and a replication sample offamilies mainly to account for the small sample sizeof the first cohort. Individual SNP analyses showedassociation with two SNPs in the case–controlstudy but not in the family sample. When these twoSNPs were combined in haplotypes, the A allele forSNP rs12666974 and the T allele for SNPrs3779262 are less frequently present amongpatients and not transmitted to the affected chil-dren in the family sample. The authors did notreport the Odds ratio or the size effect of thisgenetic contribution that most likely are low.Although mitochondrial dysfunction has beenreported in autism spectrum (8%) (2), it is notclear whether this dysfunction contributes directlyor indirectly to the susceptibility of Autism.

Similarly, this association study is the first toestablish a relationship between a mitochondrialgene and Autism. This study is based on acandidate gene for Autism and conducted in twoindependent samples, a conventional approach inmolecular genetics. Whether the results that emergefrom this study are false positive may depend onfuture studies. As the authors indicated in themanuscript, future studies will be necessary tofurther understand or confirm the role of NDUFA5in Autism. These studies may include larger samplesizes, presence of mitochondrial dysfunction, anddifferent ethnic background. Ultimately, the valid-ity of any genetic finding relies on biologicalinterpretation and experimental evidence.

Sandra VillafuerteMolecular & Behavioral Neuroscience Institute,

University of Michigan,Ann Arbor, MI, USA

E-mail: [email protected]

References

1. Marui T, Funatogawa I, Koishi S et al. The NADH-ubiqui-none oxidoreductase 1 alpha subcomplex 5 (NDUFA5)gene variants are associated with autism. Acta PsychiatrScand 2011;123:118–124.

2. Hass R. Autism and mitochondrial disease. Dev Disabil ResRev 2010;16:144–153.

Acta Psychiatr Scand 2011: 123: 95All rights reservedDOI: 10.1111/j.1600-0447.2010.01654.x

� 2011 John Wiley & Sons A/S

ACTA PSYCHIATRICASCANDINAVICA