Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents.
OBJECTIVE
There has been much focus on the potential role of mitochondria in the aetiology of type 2 diabetes and the metabolic syndrome, and many case-control mitochondrial association studies have been undertaken for these conditions. We tested for a potential association between common mitochondrial variants and a number of quantitative traits related to type 2 diabetes in a large sample of >2,000 healthy Australian adolescent twins and their siblings, many of whom were measured on more than one occasion.


METHODS
To the best of our knowledge, this is the first mitochondrial association study of quantitative traits undertaken using family data. The maternal inheritance pattern of mitochondria means established association methodologies are unsuitable for analysis of mitochondrial data in families. We present a methodology, implemented in the freely available program Sib-Pair for performing such an analysis.


RESULTS
Despite our study having the power to detect variants with modest effects on these phenotypes, only one significant association was found after correction for multiple testing in any of four age groups. This was for mt14365 with triacylglycerol levels (unadjusted p = 0.0006). This association was not replicated in other age groups.


CONCLUSIONS
We find little evidence in our sample to suggest that common European mitochondrial variants contribute to variation in quantitative phenotypes related to diabetes. Only one variant showed a significant association in our sample, and this association will need to be replicated in a larger cohort. Such replication studies or future meta-analyses may reveal more subtle effects that could not be detected here because of limitations of sample size.
Byrne
E M
EM
Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia. enda.byrne@qimr.edu.au.|Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia. enda.byrne@qimr.edu.au.|School of Medicine, University of Queensland, Brisbane, QLD, Australia. enda.byrne@qimr.edu.au.
McRae
A F
AF
Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia.|Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia.
Duffy
D L
DL
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Zhao
Z Z
ZZ
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Martin
N G
NG
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Whitfield
J B
JB
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Visscher
P M
PM
Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia.|Queensland Statistical Genetics, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD, 4029, Australia.
Montgomery
G W
GW
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005190:Family; D005260:Female; D005843:Geography; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D044469:Racial Groups; D035781:Siblings
D001786:Blood Glucose; D004272:DNA, Mitochondrial; D008055:Lipids