No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls

TY - JOUR

T1 - No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls

AU - Hudson, Gavin

AU - Panoutsopoulou, Kalliope

AU - Wilson, Ian

AU - Southam, Lorraine

AU - Rayner, Nigel W.

AU - Arden, Nigel

AU - Birrell, Fraser

AU - Carluke, Ian

AU - Carr, Andrew

AU - Chapman, Kay

AU - Deloukas, Panos

AU - Doherty, Michael

AU - McCaskie, Andrew

AU - Ollier, William E. R.

AU - Ralston, Stuart H.

AU - Reed, Mike R.

AU - Spector, Tim D.

AU - Valdes, Ana M.

AU - Wallis, Gillian A.

AU - Wilkinson, J. Mark

AU - Zeggini, Eleftheria

AU - Samuels, David C.

AU - Loughlin, John

AU - Chinnery, Patrick F.

AU - arcOGEN Consortium

PY - 2013/1

Y1 - 2013/1

N2 - Objectives Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated.Methods The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study.Results Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study.Conclusions We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.

AB - Objectives Osteoarthritis (OA) has a complex aetiology with a strong genetic component. Genome-wide association studies implicate several nuclear genes in the aetiology, but a major component of the heritability has yet to be defined at the molecular level. Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated.Methods The authors studied 138 maternally inherited mtDNA variants genotyped in a two cohort genetic association study across a total of 7393 OA cases from the arcOGEN consortium and 5122 controls genotyped in the Wellcome Trust Case Control consortium 2 study.Results Following data quality control we examined 48 mtDNA variants that were common in cohort 1 and cohort 2, and found no association with OA. None of the phenotypic subgroups previously associated with mtDNA haplogroups were associated in this study.Conclusions We were not able to replicate previously published findings in the largest mtDNA association study to date. The evidence linking OA to mtDNA is not compelling at present.

KW - HAPLOGROUPS

KW - CHONDROCYTES

KW - DYSFUNCTION

KW - DISEASE

KW - MTDNA

U2 - 10.1136/annrheumdis-2012-201932

DO - 10.1136/annrheumdis-2012-201932

M3 - Article

SN - 0003-4967

VL - 72

SP - 136

EP - 139

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 1

M1 - N/A

ER -