Context: Mitochondrial dysfunction is increasingly-implicated in pathogenesis of adult metabolic disease. Rare mitochondrial (mt) DNA mutations impair glucose homeostasis, but the contribution of common variants is unclear. In small studies, variation within the OriB origin of replication (at mt16189 in particular) has been associated with both early growth and adult metabolic phenotypes and may contribute to life-course relationships between the two.

Objective: To study a large well-characterised cohort to determine whether previously-reported small-scale associations between OriB sequence variation and early growth and adult metabolic phenotypes are robust.

Design/Setting/ Participants: Genetic association study in 5470 individuals from the population-based, Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31.

Main Outcome Measures: Indices of early growth (including birth weight, placental weight, and ponderal index) and adult metabolic homeostasis (including BMI, fasting glucose and insulin, indices of insulin action and secretion) and their relationship to variation in the OriB region.

Results: Previously-reported associations could not be confirmed. There were no significant (P < 0.01, uncorrected) associations between OriB sequence variation and measures of early growth including birthweight (P = 0.52, comparing individuals with mt16189T to those with a homopolymeric C-tract) and placental weight (P = 0.49). There were no significant associations with adult metabolic phenotypes including fasting glucose (P = 0.07), fasting insulin (P = 0.42) and homeostatic model assessment-derived measures of insulin sensitivity or secretion (P = 0.45 and P = 0.56 respectively).

Conclusion: Despite substantial power to detect previously-reported effects, mtDNA variations around OriB are not major contributors to variation in early growth and metabolic phenotypes during early adulthood.