Genetic variations related to maternal whole blood mitochondrial DNA copy number: a genome-wide and candidate gene study.
We conducted genome-wide (GWAS) and candidate gene association studies of maternal mitochondrial DNA copy number. Maternal peripheral blood was collected during labor and delivery admission from 471 participants of a placental abruption case-control study conducted in Lima, Peru. Single nucleotide polymorphism (SNP) genotyping was performed using the Illumina Cardio-Metabo Chip. Whole blood mitochondrial DNA (mtDNA) copy number was measured using qRT-PCR techniques. We evaluated 119,629 SNPs in the GWAS and 161 SNPs (in 29 mitochondrial biogenesis and oxidative phosphorylation genes) in the candidate association study. Top hits from GWAS and the candidate gene study were selected to compute weighted genetic risk scores (wGRS). Linear regression models were used to calculate effect size estimates and related nominal p values. The top hit in our GWAS was chr19:51063065 in FOXA3 (empirical p values = 2.20e - 6). A total of 134 SNPs had p values < 0.001 including rs17111633 in CNNM1 (p values = 6.32e - 6) and chr19:51083059 in MYPOP (p values = 3.23e - 5). In the candidate association study, several SNPs in PPARG, PRKCA, SP1 and THRB were associated with mtDNA copy number (p values < 0.05). mtDNA copy number was significantly associated with wGRS based on top GWAS hits (β = 0.49, 95% CI:0.38-0.60, p < 0.001). Variations in nuclear DNA are potentially associated with maternal mtDNA copy number.
a Department of Epidemiology, School of Public Health, University of Washington , Seattle, WA , USA.
Tsegaselassie
T
Workalemahu
a Department of Epidemiology, School of Public Health, University of Washington , Seattle, WA , USA.|b Center for Perinatal Studies, Swedish Medical Center , Seattle, WA , USA.
Daniel A
DA
Enquobahrie
c Department of Mathematics and Statistics, Georgetown University , Washington, DC , USA.
Mahlet G
MG
Tadesse
b Center for Perinatal Studies, Swedish Medical Center , Seattle, WA , USA.
Karin
K
Hevner
d Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA , USA.
Bizu
B
Gelaye
e Asociación Civil PROESA, Lima, Peru; Universidad Peruana de Ciencias Aplicados , Lima , Peru.
Sixto E
SE
Sanchez
d Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA , USA.
Michelle A
MA
Williams
D000037:Abruptio Placentae / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D011247:Pregnancy; D055815:Young Adult
D004272:DNA, Mitochondrial
Maternal mitochondrial DNA copy number; genetic variation; mitochondrial biogenesis; oxidative phosphorylation; pregnancy