No single rare homoplasmic variant was present at greater frequency in any disease compared to controls (Additional file
1: Figure S8). There was a trend towards a greater number of rare homoplasmic point mutations in two genes in AD compared to controls;
MT-RNR1 (AD; 30/282 (10.6%), Controls; 16/344 (4.7%)) (
p = 0.005)) and again
MT-TR (AD; 6/282 (2.1%), Controls; 0/344) (
p = 0.008), although both failed to reach significance at the corrected threshold of
p = 0.0014. (Additional file
1: Figure S8, Additional file
1: Table S5). When stratified by age, this suggested that the trend towards an excess burden of rare homoplasmic variants in
MT-RNR1 was likely driven by variants in young onset AD cases vs controls (AD: 9/53 (16.9%), Controls (2/65),
p = 0.012 (3%) (Additional file
1: Figure S9). We also saw that young onset PD-DLB cases (death aged <70) had a significantly greater number of rare homoplastic mutations in
MT-CO2 (PD-DLB: 5/23 (21.7%), Controls: 5/213 (2.3%),
p = 0.0010 (Additional file
1: Figure S9). The majority of the variants in
MT-CO2 in both cohorts were in non-coding D-loop, but when combined this did not reach the corrected threshold for significance. There was no association between any rare non-synonymous variant, nor the burden of rare non-synonymous variants in any gene or respiratory chain complex in any disease group
vs controls.