Detailed Analysis of Variation at and around Mitochondrial Position 16189 in a Large Finnish Cohort Reveals No Significant Associations with Early Growth or Metabolic Phenotypes at Age 31 Years

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: The aim was to study a large well-characterized 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: This was a genetic association study of 5470 individuals from the population-based Northern Finland Birth Cohort of 1966, followed prospectively from pregnancy to age 31 yr. Main Outcome Measures: We measured indices of early growth (including birth weight, placental weight, and ponderal index) and adult metab...