Figure 1. .

Procedure for identification and comprehensive disease-association testing of all common variants in the mtDNA coding region. 1 and 2, A total of 928 mtDNA sequences of European origin were aligned to identify 144 variants with frequency >1%. 3, tSNPs and multimarker haplotypes of tSNPs were selected to capture all 144 variant sites and haplogroups with r²⩾0.8 (a haplotype of tSNPs [shaded box] captures an untyped SNP [unshaded box]). 4, tSNPs were genotyped in a diabetic case-control panel with available metabolic phenotypes. 5, All hypotheses to be tested were enumerated. 6, Association tests were performed. 7, Studywide significance of results was assessed by permutation (multiple rounds of association testing with randomization of case-control labels or, for quantitative measures, shuffling within a population).