. Author manuscript; available in PMC: 2021 Nov 17.

Published in final edited form as: Nat Genet. 2021 May 17;53(7):982–993. doi: 10.1038/s41588-021-00868-1

Table 1. New trait-mtSNV associations defined using UKBB ICD10 and self-report codes.

Chapter	Trait	Definition	Locus	rsID, position (EA, EAF)	AA change	OR	95% CI	P (FDR)	Haplogroup
*I. Infectious and parasitic diseases*	Other specified bacterial agents*	ICD10: B968	CO1	rs879058417; 6528 (T,0.006)^G	L209L	1.36	1.18-1.57	3.1x10^-5 (0.04)	W5; K1a1b1f
*II. Neoplasm*	Skin of other and unspecified parts of face	ICD10: C443	ND3	rs41487950; 10084 (C,0.007)^I	I9T	1.36	1.17-1.57	4.7x10^-5 (0.05)	homoplastic
	Intrathoracic lymph nodes	ICD10: C771	TQ	rs41456348; 4336 (C, 002)^G	-	1.46	1.23-1.73	1.6x10^-5 (0.03)	H5a; U6d
	Descending colon	ICD10: D124	ND5	rs1556424100;12397(G,0.002)^G	T21A	1.92	1.41-2.64	4.4x10^-5 (0.05)	homoplastic
*III. Blood*	Other iron deficiency anaemias	ICD10: D50.8	TA	rs879226228; 5633 (T, 0.008)^G		1.45	1.22-1.73	2.0x10^-5 (0.04)	J2b
			CYB	rs200336777; 15812 (A,0.008)^G	V356M	1.45	1.22-1.72	3.2x10^-5 (0.03)
*IV. Endocrine, nutritional and metabolic diseases*	Hypokalaemia	ICD10: E87.6	ND2	rs367778601; 5147 (A, 0.06)^G	T226T	1.27	1.15-1.40	1.9x10^-6 (0.005)	homoplastic
	Type 2 diabetes	ICD10, ICD9, #20002, #20003	ATP6	rs2853822; 8655 (T,0.001)^Ga	I43I	1.48	1.23-1.78	3.9x10^-5 (0.05)	ancestral variant common to L
*VI. Nervous system*	Multiple sclerosis		TD	rs1556423308; 7559(G, 0.005))^I	-	2.06	1.59-2.67	5.0x10^-8 (0.0003)	K1a3a
		ICD10: G35	ND3	rs2853826; 10398 (G, 0.21)^G	T114A		1.15	1.07-1.23	4.3x10^-5 (0.05)	homoplastic
			ND5	rs878966690; 13117(G, 0.005)^G	I261V	1.65	1.30-2.11	4.2x10^-5 (0.05)	K1a3a
	Lesion of plantar nerve	ICD10: G576	CO3	rs41482146; 9667 (G, 0.01)^Ga	N154S	1.49	1.24-1.80	3.2x10^-5 (0.04)	U5a1b; J1b2a
*VII. Eye and adnexa*	Ptosis of eyelid	ICD10: H02.4	CYB	rs193302994; 15452 (A, 0.21)^G	L236I	1.15	1.07-1.23	4.8x10^-5 (0.05)	J; T
*IX. Circulatory system*	Abdominal aortic aneurysm	ICD10: I71.4	DLOOP	rs369669319; 207 (A, 0.04)^I	-	1.38	1.18-1.61	4.6x10^-5 (0.04)	homoplastic
*X. Respiratory system*	Spontaneous pneumothorax/ recurrent pneumothorax	#20002: 1126	ATP8	rs121434446; 8393 (T, 0.008)^I	P10S	1.67	1.33-2.11	1.4x10^-5 (0.02)	X2b
			TT	rs193303002; 15927 (A,0.009)^I		1.70	1.35-2.15	8.0x10^-6 (0.02)
*XI. Digestive system*	Bilateral inguinal hernia	K402	ND1	rs28357970; 3796 (G, 0.015)^G	T164A	1.43	1.22-1.67	1.2x10^-5 (0.02)	H1b1
	Volvulus	K562	ND1	rs1599988; 4216 (C, 0.21)^G	Y304H	1.23	1.12-1.35	2.1x10^-5 (0.03)	J; T
			ND4	rs869096886; 11251 (G, 0.21)^G	L164L	1.22	1.11-1.34	2.6x10^-5 (0.04)
			CYB	rs193302994; 15452 (A, 0.21)^G	L236I	1.22	1.11-1.34	3.7x10^-5 (0.05)
*XIII. Musculoskeletal system and connective tissue*	Pain in joint (Pelvic region and thigh)	ICD10: M25.55	CO1	rs201617272; 5913 (A, 0.01)^I	D4N	1.47	1.25-1.74	4.0x10^-6 (0.01)	K1b
	Other shoulder lesions	ICD10: M758	RNR1	rs200887992; 951 (A, 0.007)^I	-	1.74	1.38-2.19	2.9x10^-6 (0.008)	H2a1
	Joint disorder	#20002: 1295	ND2	rs1556422875; 4592 (C, 0.003)^I	I41I	1.91	1.44-2.53	8.2x10^-6 (0.02)	H2a5a1a; U5a1h
*XIV. Genitourinary system*	Calculus of kidney	ICD10: N20.0	ND1	rs201513497; 3736 (A, 0.001)^G	V144I	2.07	1.53-2.81	2.5x10^-6 (0.007)	C1b811b
	Urinary tract infection/kidney infection	#20002: 1196	ND4	rs1556423898; 11143(T, 0.002)^I	P128P	2.08	1.48-2.92	2.5x10^-5 (0.04)	H15a1a; U4b1a2
	Bladder problem (not cancer)	#20002: 1201	DLOOP	rs147029798; 16126 (C, 0.21)^I	-	1.12	1.06-1.17	1.3x10^-5 (0.02)	homoplastic
*XVIII. Symptoms, signs, abnormal findings*	Polyuria	ICD10: R35	CYB	rs2853504; 14793 (G, 0.05)^Ga	H16R	0.83	0.76-0.91	4.6x10^-5 (0.05)	U5a; V2a1
	Abnormal findings on diagnostic imaging of other parts of digestive tract	ICD10: R93.3	ND3	rs41487950; 10084 (C, 0.007)^I	I9T	1.68	1.32-2.14	3.1x10^-5 (0.04)	homoplastic

Summary of the single-variant mtDNA PheWas associations identified with P<5x10^-5 in UKBB (in up to 358,618 participants). Each variant had at least 10 cases carrying the effect-allele. Chapter=ICD-10 chapters. Definition: ICD-10 or non-cancer illness self-reported diseases codes. Locus=mtDNA encoded gene; rsID=SNP id as of dbSNP 153; position=mtDNA nucleotide position on rCRS (NC_012920); EA=effect allele; EAF=effect allele frequency; AA change = amino acid change. OR=odds ratio; 95% CI=95% confidence interval; P=P-value for the corresponding EA. FDR=False Discovery Rate calculated with Benjamini-Hochberg procedure. Haplogroup=Haplogroup(s) defined by the EA, according to Phylotree (build 17); SNVs tagging more than two European haplogroups are reported as “homoplastic”. G=genotyped; I=imputed; M=mixed, i.e. genotyped one array only and imputed on the other; Ga=mtSNVs genotyped on one array only (i.e. either the UKBB array or the UKBL array) and not imputed on the other array (or excluded because of low INFO score on the other array).