Schizophrenia-associated mt-DNA SNPs exhibit highly variable haplogroup affiliation and nuclear ancestry: Bi-genomic dependence raises major concerns for link to disease

被引：10

作者：

Hagen, Christian M. ^{[1
]}

Goncalves, Vanessa F. ^{[2
]}

Hedley, Paula L. ^{[1
]}

Bybjerg-Grauholm, Jonas ^{[1
]}

Baekvad-Hansen, Marie ^{[1
]}

Hansen, Christine S. ^{[1
]}

Kanters, Jurgen K. ^{[3
]}

Nielsen, Jimmi ^{[4
]}

Mors, Ole ^{[5
]}

Demur, Alfonso B. ^{[6
]}

Als, Thomas D. ^{[7
]}

Nordentoft, Merete ^{[8
]}

Borglum, Anders ^{[7
]}

Mortensen, Preben B. ^{[9
]}

Kennedy, James ^{[2
]}

Werge, Thomas M. ^{[6
]}

Hougaard, David M. ^{[1
]}

Christiansen, Michael ^{[1
,3
]}

机构：

[1] Statens Serum Inst, Dept Congenital Disorders, Copenhagen, Denmark

[2] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada

[3] Univ Copenhagen, Dept Biomed Sci, Copenhagen, Denmark

[4] Aalborg Univ Hosp, Aalborg Psychiat Hosp, Aalborg, Denmark

[5] Aarhus Univ, Dept Clin Med, Aarhus, Denmark

[6] Mental Hlth Ctr, Sct Hans, Roskilde, Denmark

[7] Aarhus Univ, Inst Med Genet, Aarhus, Denmark

[8] Mental Hlth Ctr, Roskilde, Denmark

[9] Aarhus Univ, Ctr Register Res, Inst Econ, Aarhus, Denmark

来源：

PLOS ONE | 2018年 / 13卷 / 12期

关键词：

HUMAN MITOCHONDRIAL-DNA; GENETIC-STRUCTURE; SUSCEPTIBILITY; VARIANTS; RISK; EPIDEMIOLOGY; INFLAMMATION; METAANALYSIS; DISORDERS; ALZHEIMER;

D O I：

10.1371/journal.pone.0208828

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. An analysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 Danes without a psychiatric diagnosis and 2,538 schizophrenia patients, revealed marked inter-allelic differences in mitochondrial haplogroup affiliation and nuclear ancestry. This bi-genomic dependence could entail population stratification. Only two mitochondrial SNPs, m.15043A and m.15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation and nuclear ancestry. The extensive bi-genomic dependence documented here is a major concern when interpreting historic, as well as designing future, mtDNA association studies.

引用

页数：14

共 54 条

[1] The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool [J].

Achilli, A ;

Rengo, C ;

Magri, C ;

Battaglia, V ;

Olivieri, A ;

Scozzari, R ;

Cruciani, F ;

Zeviani, M ;

Briem, E ;

Carelli, V ;

Moral, P ;

Dugoujon, JM ;

Roostalu, U ;

Loogväli, EL ;

Kivisild, T ;

Bandelt, HJ ;

Richards, M ;

Villems, R ;

Santachiara-Benerecetti, AS ;

Semino, O ;

Torroni, A .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 75 (05) :910-918

[2] Modelling the contribution of family history and variation in single nucleotide polymorphisms to risk of schizophrenia: A Danish national birth cohort-based study [J].

Agerbo, Esben ;

Mortensen, Preben B. ;

Wiuf, Carsten ;

Pedersen, Michael S. ;

McGrath, John ;

Hollegaard, Mads V. ;

Norgaard-Pedersen, Bent ;

Hougaard, David M. ;

Mors, Ole ;

Pedersen, Carsten B. .

SCHIZOPHRENIA RESEARCH, 2012, 134 (2-3) :246-252

[3]

Aidt FH, 2013, PLOS CURR, P5, DOI [10.1371/currents.hd.d891b4862929772c5a2f2a34ef1c201, DOI 10.1371/CURRENTS.HD.D891B4862929772C5A2F2A34EF1C201]

[4]

Arduino Daniela M, 2015, Methods Mol Biol, V1265, P415, DOI 10.1007/978-1-4939-2288-8_31

[5] Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity [J].

Athanasiadis, Georgios ;

Cheng, Jade Y. ;

Vilhjalmsson, Bjarni J. ;

Jorgensen, Frank G. ;

Als, Thomas D. ;

Le Hellard, Stephanie ;

Espeseth, Thomas ;

Sullivan, Patrick F. ;

Hultman, Christina M. ;

Kjaergaard, Peter C. ;

Schierup, Mikkel H. ;

Mailund, Thomas .

GENETICS, 2016, 204 (02) :711-+

[6] Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes [J].

Atilano, Shari R. ;

Malik, Deepika ;

Chwa, Marilyn ;

Caceres-Del-Carpio, Javier ;

Nesburn, Anthony B. ;

Boyer, David S. ;

Kuppermann, Baruch D. ;

Jazwinski, S. Michal ;

Miceli, Michael V. ;

Wallace, Douglas C. ;

Udar, Nitin ;

Kenney, M. Cristina .

HUMAN MOLECULAR GENETICS, 2015, 24 (16) :4491-4503

[7] Principal-Component Analysis for Assessment of Population Stratification in Mitochondrial Medical Genetics [J].

Biffi, Alessandro ;

Anderson, Christopher D. ;

Nalls, Michael A. ;

Rahman, Rosanna ;

Sonni, Akshata ;

Cortellini, Lynelle ;

Rost, Natalia S. ;

Matarin, Mar ;

Hernandez, Dena G. ;

Plourde, Anna ;

de Bakker, Paul I. W. ;

Ross, Owen A. ;

Greenberg, Steven M. ;

Furie, Karen L. ;

Meschia, James F. ;

Singleton, Andrew B. ;

Saxena, Richa ;

Rosand, Jonathan .

AMERICAN JOURNAL OF HUMAN GENETICS, 2010, 86 (06) :904-917

[8] Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: A systematic review [J].

Boonstra, Kirsten ;

Beuers, Ulrich ;

Ponsioen, Cyriel Y. .

JOURNAL OF HEPATOLOGY, 2012, 56 (05) :1181-1188

[9] MUTATION OF A NUCLEAR SUCCINATE-DEHYDROGENASE GENE RESULTS IN MITOCHONDRIAL RESPIRATORY-CHAIN DEFICIENCY [J].

BOURGERON, T ;

RUSTIN, P ;

CHRETIEN, D ;

BIRCHMACHIN, M ;

BOURGEOIS, M ;

VIEGASPEQUIGNOT, E ;

MUNNICH, A ;

ROTIG, A .

NATURE GENETICS, 1995, 11 (02) :144-149

[10] Random forests [J].

Breiman, L .

MACHINE LEARNING, 2001, 45 (01) :5-32

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