Figures and data in Associations of ABO and Rhesus D blood groups with phenome-wide disease incidence: A 41-year retrospective cohort study of 482,914 patients

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Tables
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6 figures, 3 tables and 8 additional files

Figures

Figure 1

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Selection of patients for the 41-year retrospective cohort study on ABO/RhD blood groups and associations with disease incidence in 482,914 Danish patients.

Figure 2

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Manhattan plot for blood group A with phecodes included by category.

The vertical axis shows the -log10 transformed FDR adjusted p-values on a log10-scale. The horizontal axis shows the phecodes by category. The red line indicates the statistically significant level of <0.05 for FDR adjusted p-values. Associations with p-value >0.8 are not displayed. Coloured and annotated associations were deemed statistically significant. The direction of the triangles indicates positive or inverse associations (upward: IRR >1, downward: IRR <1). The size of the triangles indicates the size of the incidence rate ratio.

Figure 3

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Manhattan plot for blood group B with phecodes included by category.

The vertical axis shows the -log10 transformed FDR adjusted p-values on a log10-scale. The horizontal axis shows the phecodes by category. The red line indicates the statistically significant level of <0.05 for FDR adjusted p-values. Associations with p-value >0.8 are not displayed. Coloured and annotated associations were deemed statistically significant. The direction of the triangles indicates positive or inverse associations (upward: IRR >1, downward: IRR <1). The size of the triangles indicates the size of the incidence rate ratio.

Figure 4

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Manhattan plot for blood group AB with phecodes included by category.

The vertical axis shows the -log10 transformed FDR adjusted p-values on a log10-scale. The horizontal axis shows the phecodes by category. The red line indicates the statistically significant level of <0.05 for FDR adjusted p-values. Associations with p-value >0.8 are not displayed. Coloured and annotated associations were deemed statistically significant. The direction of the triangles indicates positive or inverse associations (upward: IRR >1, downward: IRR <1). The size of the triangles indicates the size of the incidence rate ratio.

Figure 5

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Manhattan plot for blood group O with phecodes included by category.

The vertical axis shows the -log10 transformed FDR adjusted p-values on a log10-scale. The horizontal axis shows the phecodes by category. The red line indicates the statistically significant level of <0.05 for FDR adjusted p-values. Associations with p-value >0.8 are not displayed. Coloured and annotated associations were deemed statistically significant. The direction of the triangles indicates positive or inverse associations (upward: IRR >1, downward: IRR <1). The size of the triangles indicates the size of the incidence rate ratio.

Figure 6

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Manhattan plot for the Rhesus D blood group with phecodes included by category.

The vertical axis shows the -log10 transformed FDR adjusted p-values on a log10-scale. The horizontal axis shows the phecodes by category. The red line indicates the statistically significant level of <0.05 for FDR adjusted p-values. Associations with p-value >0.8 are not displayed. Coloured and annotated associations were deemed statistically significant. The direction of the triangles indicates positive or inverse associations (upward: IRR >1, downward: IRR <1). The size of the triangles indicates the size of the incidence rate ratio.

Tables

Table 1

Characteristics of patients in the 41-year retrospective cohort study on ABO/RhD blood groups and associations with disease incidence in 482,914 Danish patients.

		N=482,914
ABO, n (%)	O	197,634 (40.9)
	A	206,110 (42.7)
	AB	22,111 (4.6)
	B	57,059 (11.8)
RhD, n (%)	Negative	74,150 (15.4)
RhD, n (%)	Positive	408,764 (84.6)
Sex, n (%)	K	291,649 (60.4)
Sex, n (%)	M	191,265 (39.6)
Birth year, median [Q1,Q3]		1963 [1945,1982]
Age at entry, median [Q1,Q3]		13 [0,32]
Follow-up time, median [Q1,Q3]		40.8 [33.4,41.3]

Table 2

Statistically significant incidence rate ratios for each individual blood group A, B, AB, and O relative to any other blood group (e.g. A vs. B, AB, and O combined). Further, also for RhD-positive blood group relative to the RhD negative blood group.

				Blood group A		Blood group B		Blood group AB		Blood group 0		Blood group RhD
Phecode	Phenotype	Cases	Person-years	IRR (95% CI)	p-value	IRR (95% CI)	p-value	IRR (95% CI)	p-value	IRR (95% CI)	p-value	IRR (95% CI)	p-value
Infectious Diseases
010	Tuberculosis	2101	17603440	0.87 (0.74, 1.02)	0.093	1.4 (1.18, 1.65)	<0.001	1.07 (0.32, 3.57)	0.915	0.97 (0.59, 1.57)	0.899	1.36 (1.12, 1.65)	0.002
070	Viral hepatitis	6596	17557078	0.88 (0.82, 0.93)	<0.001	1.22 (1.12, 1.34)	<0.001	1 (0.81, 1.23)	0.97	1.04 (0.9, 1.21)	0.583	1.12 (0.99, 1.28)	0.069
070.2	Viral hepatitis B	1664	17613572	0.7 (0.62, 0.79)	<0.001	1.66 (1.46, 1.9)	<0.001	1.12 (0.38, 3.26)	0.851	1.06 (0.7, 1.61)	0.794	1.36 (1.07, 1.71)	0.01
071	Human immunodeficiency virus [HIV] disease	1182	17620808	0.81 (0.63, 1.05)	0.109	1.18 (0.54, 2.59)	0.688	1.19 (0.52, 2.73)	0.693	1.1 (0.67, 1.81)	0.725	1.49 (1.04, 2.15)	0.031
071.1	HIV infection, symptomatic	1182	17620808	0.81 (0.63, 1.05)	0.109	1.18 (0.54, 2.59)	0.688	1.19 (0.52, 2.73)	0.693	1.1 (0.67, 1.81)	0.725	1.49 (1.04, 2.15)	0.031
110.13	Dermatophytosis of the body	211	17630531	0.89 (0.35, 2.22)	0.809	1.64 (1.08, 2.49)	0.02	0.93 (0.03, 30.15)	0.97	0.88 (0.35, 2.23)	0.804	1.13 (0.2, 6.46)	0.897
Neoplasms
145.2	Cancer of tongue	606	17629055	0.95 (0.51, 1.76)	0.877	1.13 (0.71, 1.82)	0.616	1.21 (0.43, 3.38)	0.726	0.96 (0.46, 2.03)	0.93	0.74 (0.6, 0.92)	0.007
157	Pancreatic cancer	2828	17627948	1.26 (1.16, 1.36)	<0.001	1.02 (0.34, 3.13)	0.97	1.11 (0.53, 2.33)	0.8	0.76 (0.7, 0.82)	<0.001	1.01 (0.52, 1.98)	0.97
180	Cervical cancer and dysplasia	12538	10308860	1.05 (0.99, 1.12)	0.118	0.9 (0.83, 0.97)	0.01	0.96 (0.66, 1.39)	0.839	1 (0.99, 1.01)	0.97	0.93 (0.86, 1.01)	0.083
180.3	Cervical intraepithelial neoplasia [CIN] [Cervical dysplasia]	10895	10327107	1.06 (0.99, 1.13)	0.115	0.89 (0.82, 0.97)	0.009	0.95 (0.67, 1.34)	0.766	1 (0.84, 1.19)	0.97	0.93 (0.85, 1.01)	0.102
195.1	Malignant neoplasm, other	7383	17603424	0.96 (0.87, 1.05)	0.368	0.95 (0.77, 1.17)	0.642	0.96 (0.55, 1.69)	0.906	1.07 (1, 1.15)	0.038	0.88 (0.82, 0.94)	<0.001
204.3	Monocytic leukemia	179	17631300	1.04 (0.15, 7.27)	0.97	0.92 (0.06, 13.67)	0.957	0.25 (0.06, 0.98)	0.047	1.13 (0.44, 2.91)	0.809	0.84 (0.37, 1.93)	0.698
216	Benign neoplasm of skin	12993	17495431	1.02 (0.84, 1.23)	0.883	0.9 (0.82, 0.98)	0.014	0.99 (0.62, 1.57)	0.97	1.03 (0.93, 1.14)	0.583	0.95 (0.85, 1.05)	0.32
860	Bone marrow or stem cell transplant	142	17631302	1.01 (0.77, 1.31)	0.97	0.63 (0.15, 2.57)	0.531	0.15 (0.05, 0.44)	<0.001	1.37 (1.02, 1.82)	0.033	4.15 (2.13, 8.09)	<0.001
Endocrine/Metabolic
242	Thyrotoxicosis with or without goiter	9744	17527426	0.93 (0.86, 1.02)	0.127	0.99 (0.59, 1.65)	0.97	0.9 (0.66, 1.22)	0.505	1.09 (1.02, 1.18)	0.013	1.02 (0.7, 1.48)	0.927
250	Diabetes mellitus	36810	17295033	1.01 (0.92, 1.11)	0.849	1.09 (1.05, 1.13)	<0.001	1.06 (0.95, 1.18)	0.32	0.95 (0.92, 0.97)	<0.001	1.07 (1.03, 1.11)	<0.001
250.2	Type 2 diabetes	32505	17346533	1 (0.82, 1.23)	0.97	1.1 (1.06, 1.15)	<0.001	1.07 (0.96, 1.19)	0.213	0.94 (0.92, 0.97)	<0.001	1.07 (1.02, 1.12)	0.004
261	Vitamin deficiency	6674	17594082	0.94 (0.86, 1.03)	0.183	1.15 (1.05, 1.26)	0.003	0.93 (0.66, 1.31)	0.683	1.01 (0.75, 1.36)	0.94	1.06 (0.92, 1.22)	0.405
261.4	Vitamin D deficiency	4105	17613013	0.91 (0.85, 0.97)	0.007	1.23 (1.14, 1.34)	<0.001	0.95 (0.56, 1.61)	0.86	1.01 (0.63, 1.63)	0.97	1.14 (1.04, 1.25)	0.006
271	Disorders of carbohydrate transport and metabolism	1306	17619038	0.86 (0.69, 1.07)	0.176	1.28 (1, 1.64)	0.047	1.07 (0.23, 4.92)	0.934	1.01 (0.51, 2)	0.97	1.16 (0.78, 1.72)	0.475
271.3	Intestinal disaccharidase deficiencies and disaccharide malabsorption	1154	17621337	0.85 (0.68, 1.05)	0.135	1.32 (1.05, 1.67)	0.018	1.08 (0.24, 4.88)	0.924	1.01 (0.55, 1.86)	0.97	1.15 (0.73, 1.8)	0.562
272	Disorders of lipoid metabolism	41222	17347032	1.06 (1.03, 1.09)	<0.001	1.01 (0.72, 1.42)	0.97	1.03 (0.63, 1.69)	0.92	0.93 (0.91, 0.96)	<0.001	1.02 (0.9, 1.17)	0.733
272.11	Hypercholesterolemia	35565	17395012	1.06 (1.03, 1.09)	<0.001	1.01 (0.79, 1.29)	0.956	1.03 (0.88, 1.21)	0.709	0.93 (0.91, 0.96)	<0.001	1.03 (0.96, 1.09)	0.433
272.13	Mixed hyperlipidemia	1324	17619911	1.05 (0.66, 1.67)	0.841	1.04 (0.14, 7.94)	0.97	1.39 (1.01, 1.91)	0.04	0.87 (0.7, 1.08)	0.211	1.09 (0.58, 2.04)	0.809
Hematopoietic
282	Hereditary hemolytic anemias	947	482914*	0.76 (0.59, 0.99)**	0.039	1.36 (0.9, 2.06)**	0.141	1.42 (0.72, 2.8)**	0.316	1.03 (0.25, 4.26)**	0.97	1.65 (1.06, 2.56)**	0.026
282.8	Other hemoglobinopathies	557	482914*	0.65 (0.51, 0.82)**	<0.001	1.56 (1.16, 2.1)**	0.003	1.47 (0.77, 2.83)**	0.248	1.09 (0.58, 2.07)**	0.798	2.24 (1.52, 3.29)**	<0.001
286	Coagulation defects	4124	17606796	1.14 (1.01, 1.3)	0.035	0.95 (0.56, 1.6)	0.854	1.14 (0.67, 1.95)	0.633	0.87 (0.76, 0.99)	0.029	0.93 (0.66, 1.33)	0.717
286.11	Von willebrand’s disease	214	482914*	0.71 (0.35, 1.47)**	0.368	0.49 (0.17, 1.45)**	0.199	0.39 (0.02, 8.74)**	0.562	1.96 (1.32, 2.91)**	<0.001	0.68 (0.29, 1.6)**	0.388
286.3	Coagulation defects complicating pregnancy or postpartum	2015	10502418	1.15 (1.08, 1.22)	<0.001	1.02 (0.58, 1.79)	0.946	1.14 (0.95, 1.38)	0.164	0.84 (0.79, 0.89)	<0.001	0.88 (0.8, 0.97)	0.013
286.7	Other and unspecified coagulation defects	1085	17621421	1.23 (1.05, 1.45)	0.013	0.98 (0.45, 2.16)	0.97	1.52 (1.1, 2.08)	0.011	0.74 (0.64, 0.85)	<0.001	1.03 (0.23, 4.72)	0.97
Mental Disorders
300.1	Anxiety disorder	7985	17603188	1.03 (0.93, 1.14)	0.575	0.97 (0.8, 1.16)	0.735	0.96 (0.66, 1.41)	0.858	0.99 (0.76, 1.29)	0.953	0.92 (0.86, 0.99)	0.027
Neurological
333.8	Other degenerative diseases of the basal ganglia	381	17630209	0.78 (0.57, 1.07)	0.128	1.05 (0.11, 9.95)	0.967	0.65 (0.24, 1.78)	0.407	1.32 (1.02, 1.71)	0.033	1 (0.95, 1.05)	0.97
339	Other headache syndromes	3466	17603269	1.05 (0.9, 1.22)	0.546	1.11 (0.95, 1.3)	0.204	1.03 (0.39, 2.73)	0.957	0.9 (0.83, 0.99)	0.023	1.06 (0.82, 1.36)	0.688
345	Epilepsy, recurrent seizures, convulsions	23469	17228780	0.99 (0.77, 1.28)	0.97	0.96 (0.86, 1.08)	0.51	0.97 (0.71, 1.32)	0.853	1.03 (0.96, 1.1)	0.44	0.94 (0.89, 1)	0.039
345.3	Convulsions	14391	17351676	0.99 (0.76, 1.3)	0.97	0.96 (0.79, 1.18)	0.732	1 (0.88, 1.13)	0.97	1.02 (0.89, 1.18)	0.77	0.92 (0.85, 0.99)	0.036
Sense Organs
361.1	Retinal detachment with retinal defect	3037	17594394	1.06 (0.87, 1.29)	0.582	1.07 (0.69, 1.66)	0.787	1.23 (0.9, 1.69)	0.193	0.88 (0.79, 0.98)	0.022	0.97 (0.49, 1.96)	0.948
381	Otitis media and Eustachian tube disorders	22790	17144551	1.07 (1.03, 1.11)	<0.001	0.94 (0.86, 1.04)	0.226	1.01 (0.55, 1.87)	0.97	0.95 (0.91, 1)	0.039	0.96 (0.87, 1.06)	0.437
381.1	Otitis media	12313	17364091	1.09 (1.04, 1.14)	<0.001	0.95 (0.83, 1.09)	0.449	0.98 (0.44, 2.22)	0.97	0.94 (0.89, 1)	0.067	0.97 (0.82, 1.13)	0.688
381.2	Eustachian tube disorders	2358	17571118	1.15 (1.01, 1.31)	0.033	0.9 (0.62, 1.29)	0.566	0.87 (0.38, 2.01)	0.765	0.93 (0.74, 1.17)	0.531	0.88 (0.69, 1.13)	0.32
385.5	Tympanosclerosis and middle ear disease related to otitis media	530	17625215	1.25 (0.95, 1.64)	0.114	0.99 (0.55, 1.77)	0.97	1.21 (0.37, 3.96)	0.761	0.77 (0.6, 0.98)	0.036	1.08 (0.29, 3.98)	0.918
386.9	Dizziness and giddiness (Light-headedness and vertigo)	1060	17624097	0.84 (0.73, 0.97)	0.016	1.04 (0.43, 2.55)	0.933	0.82 (0.42, 1.57)	0.555	1.2 (1.06, 1.37)	0.005	1.08 (0.7, 1.68)	0.738
389	Hearing loss	43238	17166114	0.99 (0.88, 1.12)	0.897	1.01 (0.74, 1.37)	0.97	1.01 (0.78, 1.3)	0.97	1.01 (0.83, 1.21)	0.96	1.06 (1.01, 1.1)	0.009
389.3	Degenerative and vascular disorders of ear	22354	17419947	0.99 (0.81, 1.22)	0.94	1 (0.85, 1.19)	0.97	1.02 (0.53, 1.94)	0.961	1 (0.83, 1.22)	0.97	1.08 (1.02, 1.15)	0.012
Circulatory System
394	Rheumatic disease of the heart valves	8422	17577658	1.08 (1.01, 1.16)	0.029	0.98 (0.61, 1.57)	0.924	0.93 (0.63, 1.38)	0.744	0.94 (0.86, 1.03)	0.2	0.96 (0.78, 1.19)	0.729
411.2	Myocardial infarction	25905	17411193	1.03 (0.96, 1.11)	0.434	1.06 (0.97, 1.16)	0.188	1.03 (0.58, 1.8)	0.932	0.94 (0.9, 0.98)	0.008	1.02 (0.83, 1.26)	0.867
415	Pulmonary heart disease	10870	17565369	1.2 (1.15, 1.26)	<0.001	1.07 (0.9, 1.27)	0.475	1.14 (0.96, 1.36)	0.125	0.78 (0.75, 0.82)	<0.001	0.95 (0.82, 1.09)	0.482
415.11	Pulmonary embolism and infarction, acute	1533	17612465	1.39 (1.21, 1.59)	<0.001	1.11 (0.56, 2.18)	0.781	1.14 (0.44, 2.98)	0.798	0.65 (0.57, 0.75)	<0.001	0.88 (0.59, 1.32)	0.562
425.12	Other hypertrophic cardiomyopathy	466	17628820	0.81 (0.61, 1.07)	0.138	0.83 (0.35, 1.98)	0.683	1.11 (0.12, 10.23)	0.93	1.3 (1.03, 1.64)	0.028	0.91 (0.32, 2.6)	0.877
428.1	Congestive heart failure (CHF) NOS	8357	17595328	1.03 (0.94, 1.13)	0.5	1.02 (0.76, 1.37)	0.906	1.12 (0.96, 1.3)	0.14	0.94 (0.89, 0.99)	0.028	1.01 (0.7, 1.46)	0.961
440	Atherosclerosis	10901	17554704	1.05 (0.95, 1.16)	0.345	1.1 (0.96, 1.25)	0.169	1.12 (0.91, 1.37)	0.3	0.9 (0.85, 0.95)	<0.001	1.04 (0.88, 1.23)	0.675
440.2	Atherosclerosis of the extremities	8348	17570336	1.06 (0.96, 1.18)	0.258	1.09 (0.9, 1.32)	0.406	1.08 (0.75, 1.55)	0.686	0.9 (0.84, 0.96)	0.002	1.03 (0.8, 1.33)	0.823
442.2	Aneurysm of iliac artery	326	17630660	0.75 (0.64, 0.89)	<0.001	1.13 (0.63, 2.04)	0.69	1.2 (0.61, 2.38)	0.607	1.21 (1, 1.47)	0.045	0.72 (0.6, 0.87)	<0.001
443	Peripheral vascular disease	13791	17546796	1.05 (0.98, 1.12)	0.153	1.01 (0.59, 1.73)	0.97	1.03 (0.71, 1.5)	0.872	0.94 (0.89, 1)	0.035	1.03 (0.91, 1.18)	0.63
443.7	Peripheral angiopathy in diseases classified elsewhere	3677	17611414	1.02 (0.68, 1.51)	0.94	1.1 (0.9, 1.34)	0.37	1.1 (0.78, 1.55)	0.603	0.93 (0.83, 1.04)	0.214	1.18 (1.05, 1.31)	0.004
444	Arterial embolism and thrombosis	2390	17614619	1.14 (0.98, 1.34)	0.093	1.11 (0.77, 1.61)	0.583	1.28 (0.93, 1.76)	0.134	0.79 (0.7, 0.89)	<0.001	1 (0.92, 1.08)	0.97
444.1	Arterial embolism and thrombosis of lower extremity artery	1286	17623872	1.13 (0.78, 1.63)	0.533	1.13 (0.61, 2.13)	0.706	1.38 (0.86, 2.23)	0.185	0.78 (0.63, 0.97)	0.022	0.98 (0.35, 2.76)	0.97
451	Phlebitis and thrombophlebitis	16748	17479709	1.22 (1.18, 1.25)	<0.001	1.15 (1.09, 1.21)	<0.001	1.29 (1.18, 1.4)	<0.001	0.73 (0.7, 0.75)	<0.001	0.97 (0.84, 1.13)	0.717
451.2	Phlebitis and thrombophlebitis of lower extremities	15650	17489528	1.23 (1.19, 1.27)	<0.001	1.14 (1.08, 1.2)	<0.001	1.31 (1.2, 1.42)	<0.001	0.72 (0.69, 0.74)	<0.001	0.97 (0.84, 1.12)	0.678
452	Other venous embolism and thrombosis	4275	17607194	1.24 (1.16, 1.32)	<0.001	1.21 (1.07, 1.36)	0.002	1.31 (1.1, 1.56)	0.003	0.69 (0.64, 0.74)	<0.001	1 (0.89, 1.11)	0.97
452.8	Postphlebitic syndrome	341	17629425	1.35 (1.08, 1.68)	0.009	1.26 (0.76, 2.08)	0.378	1.82 (1.13, 2.94)	0.014	0.55 (0.45, 0.67)	<0.001	1.18 (0.54, 2.56)	0.688
454	Varicose veins	16500	17381971	1.1 (1.01, 1.2)	0.032	0.98 (0.57, 1.68)	0.946	1.04 (0.51, 2.1)	0.93	0.91 (0.83, 1)	0.05	0.98 (0.67, 1.42)	0.906
455	Hemorrhoids	9001	17523962	0.95 (0.84, 1.08)	0.481	0.91 (0.78, 1.08)	0.279	0.91 (0.67, 1.24)	0.562	1.1 (1.03, 1.18)	0.005	0.99 (0.67, 1.46)	0.97
456	Chronic venous insufficiency [CVI]	925	17626709	1.24 (1.07, 1.44)	0.004	1.04 (0.23, 4.7)	0.967	1.37 (0.91, 2.05)	0.131	0.73 (0.64, 0.83)	<0.001	0.94 (0.49, 1.79)	0.858
459	Other disorders of circulatory system	2555	17616713	1.12 (0.99, 1.27)	0.076	1.12 (0.85, 1.48)	0.433	1.15 (0.75, 1.75)	0.528	0.82 (0.75, 0.9)	<0.001	1.08 (0.8, 1.46)	0.636
459.9	Circulatory disease NEC	2174	17618930	1.16 (1.02, 1.31)	0.024	1.13 (0.86, 1.5)	0.381	1.22 (0.85, 1.74)	0.279	0.78 (0.71, 0.86)	<0.001	1.02 (0.38, 2.74)	0.966
Respiratory
474	Acute and chronic tonsillitis	41427	16817602	1.1 (1.08, 1.13)	<0.001	0.93 (0.88, 0.97)	0.002	1.01 (0.63, 1.63)	0.97	0.94 (0.91, 0.96)	<0.001	0.97 (0.9, 1.05)	0.466
474.2	Chronic tonsillitis and adenoiditis	27077	17030480	1.14 (1.11, 1.17)	<0.001	0.89 (0.84, 0.93)	<0.001	1.02 (0.75, 1.4)	0.897	0.92 (0.89, 0.94)	<0.001	0.96 (0.89, 1.03)	0.259
477	Epistaxis or throat hemorrhage	12337	17506794	0.93 (0.89, 0.98)	0.006	0.92 (0.83, 1.02)	0.118	0.94 (0.71, 1.23)	0.648	1.12 (1.08, 1.16)	<0.001	1.01 (0.73, 1.41)	0.948
495	Asthma	31106	17238738	1.04 (1, 1.08)	0.028	0.94 (0.88, 0.99)	0.023	1 (1, 1)	0.97	0.99 (0.9, 1.08)	0.777	0.99 (0.78, 1.27)	0.97
Digestive
530.11	GERD	7461	17582158	0.99 (0.69, 1.43)	0.966	1.12 (1.03, 1.22)	0.007	1.04 (0.62, 1.72)	0.897	0.95 (0.88, 1.03)	0.223	1.12 (1.03, 1.21)	0.007
530.7	Gastroesophageal laceration-hemorrhage syndrome	597	17623900	1.16 (0.8, 1.66)	0.439	1.04 (0.15, 7.23)	0.97	0.43 (0.22, 0.83)	0.012	0.94 (0.44, 2.02)	0.883	1.09 (0.39, 2.99)	0.883
531	Peptic ulcer (excl. esophageal)	16678	17443704	0.9 (0.87, 0.94)	<0.001	1 (0.94, 1.07)	0.97	0.92 (0.75, 1.14)	0.471	1.12 (1.08, 1.16)	<0.001	1.02 (0.83, 1.25)	0.86
531.1	Hemorrhage from gastrointestinal ulcer	6277	17583751	0.91 (0.84, 0.98)	0.009	0.89 (0.75, 1.04)	0.149	0.91 (0.6, 1.4)	0.688	1.17 (1.11, 1.25)	<0.001	1.07 (0.91, 1.27)	0.421
531.2	Gastric ulcer	6745	17555312	0.91 (0.85, 0.98)	0.008	1.01 (0.63, 1.63)	0.97	0.92 (0.62, 1.36)	0.681	1.11 (1.04, 1.18)	0.002	0.97 (0.73, 1.28)	0.838
531.3	Duodenal ulcer	4534	17555684	0.88 (0.8, 0.96)	0.007	1.06 (0.71, 1.57)	0.803	0.97 (0.21, 4.56)	0.97	1.12 (1.01, 1.24)	0.028	1.05 (0.77, 1.43)	0.789
531.5	Gastrojejunal ulcer	586	17628539	0.83 (0.61, 1.11)	0.213	1.41 (1.08, 1.84)	0.012	1.12 (0.23, 5.41)	0.897	1.01 (0.64, 1.6)	0.97	0.85 (0.56, 1.28)	0.439
550	Abdominal hernia	47761	16976073	1.01 (0.94, 1.09)	0.757	0.94 (0.89, 0.99)	0.021	0.97 (0.81, 1.17)	0.765	1.02 (0.96, 1.08)	0.575	1.01 (0.77, 1.32)	0.97
562	Diverticulosis and diverticulitis	16569	17515568	0.94 (0.87, 1.03)	0.19	0.92 (0.82, 1.03)	0.138	0.91 (0.7, 1.18)	0.481	1.11 (1.06, 1.17)	<0.001	0.98 (0.75, 1.28)	0.884
562.1	Diverticulosis	16569	17515568	0.94 (0.87, 1.03)	0.19	0.92 (0.82, 1.03)	0.138	0.91 (0.7, 1.18)	0.481	1.11 (1.06, 1.17)	<0.001	0.98 (0.75, 1.28)	0.884
571.81	Portal hypertension	1101	17627608	0.94 (0.66, 1.35)	0.766	1.17 (0.83, 1.63)	0.376	0.62 (0.43, 0.9)	0.011	1.06 (0.76, 1.47)	0.746	0.99 (0.52, 1.88)	0.97
574	Cholelithiasis and cholecystitis	31530	17299206	1.05 (1.02, 1.09)	0.004	0.98 (0.85, 1.13)	0.766	0.99 (0.64, 1.53)	0.97	0.96 (0.92, 1)	0.062	1.01 (0.73, 1.39)	0.957
574.1	Cholelithiasis	24028	17364917	1.05 (1.01, 1.1)	0.029	0.98 (0.81, 1.18)	0.809	0.99 (0.49, 1.96)	0.97	0.96 (0.91, 1.02)	0.183	1.01 (0.75, 1.35)	0.97
574.12	Cholelithiasis with other cholecystitis	2650	17605642	1.12 (1, 1.25)	0.044	0.88 (0.69, 1.12)	0.32	0.91 (0.48, 1.7)	0.77	0.95 (0.76, 1.2)	0.688	0.96 (0.61, 1.52)	0.878
574.2	Calculus of bile duct	8401	17560937	1.07 (1, 1.15)	0.042	0.95 (0.78, 1.17)	0.651	0.98 (0.46, 2.06)	0.953	0.95 (0.87, 1.05)	0.33	1.07 (0.94, 1.21)	0.32
575.2	Obstruction of bile duct	1593	17626684	1.24 (1.1, 1.41)	<0.001	0.97 (0.28, 3.43)	0.97	1.04 (0.18, 5.91)	0.97	0.8 (0.7, 0.91)	0.001	1.1 (0.71, 1.69)	0.688
578	Gastrointestinal hemorrhage	20111	17502200	0.96 (0.9, 1.03)	0.296	0.94 (0.83, 1.08)	0.393	0.91 (0.78, 1.07)	0.249	1.08 (1.03, 1.12)	<0.001	1.01 (0.77, 1.33)	0.93
578.8	Hemorrhage of rectum and anus	11095	17555331	0.96 (0.87, 1.06)	0.413	0.93 (0.79, 1.1)	0.395	0.92 (0.71, 1.18)	0.505	1.09 (1.03, 1.15)	0.004	1 (0.8, 1.26)	0.97
Genitourinary
614.51	Cervicitis and endocervicitis	660	10488791	0.97 (0.52, 1.8)	0.918	1.1 (0.7, 1.73)	0.696	1.4 (1.03, 1.91)	0.033	0.93 (0.64, 1.34)	0.706	1.16 (0.86, 1.57)	0.326
622.2	Mucous polyp of cervix	1401	10498802	1.17 (1.03, 1.34)	0.02	0.99 (0.64, 1.53)	0.97	1.12 (0.56, 2.21)	0.766	0.83 (0.73, 0.95)	0.007	0.97 (0.43, 2.18)	0.948
626.12	Excessive or frequent menstruation	10504	10375823	0.92 (0.86, 0.99)	0.026	0.96 (0.74, 1.24)	0.757	1.02 (0.48, 2.14)	0.97	1.1 (1.03, 1.17)	0.004	0.97 (0.76, 1.23)	0.811
Pregnancy Complications
634.3	Ectopic pregnancy	5034	10426967	0.97 (0.87, 1.08)	0.592	1.11 (1.01, 1.21)	0.022	1.11 (0.93, 1.34)	0.25	0.96 (0.86, 1.08)	0.524	0.99 (0.65, 1.5)	0.957
643	Excessive vomiting in pregnancy	4314	10470323	0.91 (0.85, 0.97)	0.005	1.17 (1.08, 1.27)	<0.001	1.12 (0.83, 1.51)	0.48	1 (0.87, 1.14)	0.97	1 (0.89, 1.11)	0.97
643.1	Hyperemesis gravidarum	3558	10488446	0.9 (0.84, 0.96)	0.002	1.15 (0.97, 1.37)	0.105	1.11 (0.91, 1.37)	0.313	1.01 (0.76, 1.36)	0.927	1.05 (0.78, 1.4)	0.777
647.3	Major puerperal infection	274	10504689	1.04 (0.34, 3.13)	0.952	1.37 (0.98, 1.92)	0.068	0.78 (0.25, 2.45)	0.688	0.86 (0.59, 1.25)	0.439	0.72 (0.56, 0.93)	0.01
649.1	Diabetes or abnormal glucose tolerance complicating pregnancy	5053	10480682	0.92 (0.64, 1.33)	0.679	1.22 (0.95, 1.56)	0.118	1.17 (0.75, 1.82)	0.504	0.95 (0.55, 1.64)	0.866	1.26 (1.03, 1.55)	0.026
654.1	Abnormality of organs and soft tissues of pelvis complicating pregnancy, childbirth, or the puerperium	5842	10479533	0.94 (0.89, 0.99)	0.016	1.09 (1.01, 1.16)	0.019	0.93 (0.76, 1.13)	0.467	1.04 (0.96, 1.12)	0.378	1.08 (1.01, 1.16)	0.03
654.2	Rhesus isoimmunization in pregnancy	808	10503190	1.12 (0.91, 1.38)	0.294	0.8 (0.61, 1.06)	0.118	0.82 (0.4, 1.71)	0.612	1.01 (0.65, 1.57)	0.97	0.26 (0.24, 0.29)	<0.001
656.1	Isoimmunization of fetus or newborn	508	482914*	2.6 (1.57, 4.33)**	<0.001	1.57 (0.53, 4.61)**	0.42	0.4 (0.01, 11.01)**	0.599	0.24 (0.11, 0.51)**	<0.001	1.03 (0.21, 5.13)**	0.97
Dermatologic
704	Diseases of hair and hair follicles	4102	17578353	0.99 (0.62, 1.59)	0.97	1.18 (1.04, 1.34)	0.01	1.03 (0.25, 4.3)	0.97	0.93 (0.82, 1.06)	0.273	1.04 (0.68, 1.59)	0.876
704.2	Hirsutism	1778	17608888	0.94 (0.7, 1.26)	0.688	1.32 (1.15, 1.5)	<0.001	1.26 (0.96, 1.65)	0.093	0.88 (0.75, 1.04)	0.13	1.13 (0.87, 1.45)	0.369
707	Chronic ulcer of skin	2121	17617533	0.94 (0.74, 1.19)	0.617	1.23 (1.04, 1.47)	0.017	0.94 (0.29, 3.07)	0.927	0.98 (0.51, 1.88)	0.959	1.01 (0.59, 1.74)	0.97
Musculoskeletal
722.7	Intervertebral disc disorder with myelopathy	747	17625461	0.95 (0.61, 1.47)	0.82	1.26 (1.01, 1.59)	0.042	0.65 (0.31, 1.35)	0.248	1.01 (0.58, 1.76)	0.97	0.97 (0.28, 3.31)	0.961
727	Other disorders of synovium, tendon, and bursa	30487	17272753	1.02 (0.95, 1.09)	0.627	0.94 (0.89, 0.99)	0.016	0.99 (0.57, 1.7)	0.97	1.01 (0.92, 1.11)	0.809	0.97 (0.9, 1.04)	0.352
727.7	Contracture of tendon (sheath)	391	17628006	0.91 (0.45, 1.84)	0.8	1.14 (0.38, 3.43)	0.826	1.11 (0.05, 24.01)	0.951	1.02 (0.46, 2.25)	0.97	0.65 (0.47, 0.9)	0.009
728	Disorders of muscle, ligament, and fascia	11338	17510763	1.08 (1.02, 1.13)	0.008	0.93 (0.83, 1.04)	0.199	0.88 (0.74, 1.05)	0.164	0.98 (0.85, 1.12)	0.766	0.93 (0.85, 1.01)	0.085
740	Osteoarthrosis	53711	17187748	1.01 (0.94, 1.09)	0.815	0.95 (0.9, 0.99)	0.021	1.02 (0.79, 1.31)	0.911	1.01 (0.93, 1.1)	0.838	0.97 (0.92, 1.01)	0.132
740.11	Osteoarthrosis, localized, primary	40386	17333061	1.01 (0.94, 1.09)	0.779	0.94 (0.9, 0.99)	0.012	0.99 (0.72, 1.35)	0.94	1.01 (0.95, 1.08)	0.663	0.97 (0.92, 1.02)	0.188
741	Symptoms and disorders of the joints	5085	17578450	0.99 (0.66, 1.48)	0.97	0.85 (0.73, 0.99)	0.032	0.93 (0.52, 1.69)	0.83	1.09 (0.99, 1.2)	0.072	1 (0.82, 1.24)	0.97
742	Derangement of joint, non-traumatic	16652	17438176	1.03 (0.96, 1.11)	0.357	0.9 (0.83, 0.97)	0.004	0.98 (0.61, 1.56)	0.924	1.02 (0.88, 1.17)	0.838	0.95 (0.87, 1.04)	0.291
742.9	Other derangement of joint	13669	17490182	1.02 (0.9, 1.16)	0.757	0.91 (0.83, 0.99)	0.023	0.98 (0.47, 2.06)	0.97	1.02 (0.91, 1.15)	0.714	0.95 (0.86, 1.04)	0.26
743	Osteoporosis, osteopenia and pathological fracture	15875	17536424	1.05 (1, 1.11)	0.049	0.94 (0.85, 1.05)	0.26	0.92 (0.76, 1.12)	0.405	0.99 (0.85, 1.14)	0.858	1 (0.98, 1.02)	0.97
743.11	Osteoporosis NOS	13633	17553976	1.06 (1.02, 1.1)	0.003	0.93 (0.87, 1)	0.039	0.94 (0.78, 1.13)	0.514	0.98 (0.9, 1.07)	0.68	1 (0.82, 1.21)	0.97
Congenital Anomalies
747	Cardiac and circulatory congenital anomalies	15297	482914*	1.07 (1.01, 1.14)**	0.029	0.94 (0.8, 1.11)**	0.475	1.02 (0.47, 2.23)**	0.961	0.95 (0.88, 1.03)**	0.223	0.98 (0.77, 1.25)**	0.884
747.1	Cardiac congenital anomalies	1621	482914*	1.19 (1.02, 1.39)**	0.023	0.77 (0.6, 0.98)**	0.036	1.03 (0.27, 3.86)**	0.97	0.93 (0.69, 1.25)**	0.635	1.02 (0.48, 2.16)**	0.97
755	Congenital anomalies of limbs	6557	482914*	0.99 (0.65, 1.5)**	0.957	0.96 (0.71, 1.29)**	0.778	0.96 (0.46, 1.97)**	0.91	1.04 (0.89, 1.23)**	0.627	0.88 (0.8, 0.97)**	0.013
755.61	Congenital hip dysplasia and deformity	2823	482914*	1.01 (0.57, 1.78)**	0.97	0.87 (0.66, 1.16)**	0.355	0.89 (0.42, 1.88)**	0.766	1.07 (0.85, 1.35)**	0.57	0.81 (0.71, 0.94)**	0.004

a. Statistically significant IRRs are marked with bold (FDR adjusted P-value <0.05).
b. The IRRs are adjusted for age, sex, interaction between age and sex, and birth year.
c. All other ABO blood groups and the RhD negative blood group was used as a reference, respectively.
d. FDR-adjusted p-values and 95% confidence intervals are presented.
e. FDR adjusted p-values above 0.97 were set to 0.97 to avoid exploding adjusted confidence intervals.
e. Phecodes are divided by PheWAS disease categories.
f. The number of events and the follow-up time in person-years for each phecode is presented.
g. For study results of congenital phecodes estimates marked with ** are prevalence ratios instead of IRRs and the corresponding person-year marked with * are the size of the cohort.

Table 2—source data 1 Associations between the ABO/RhD blood groups and phecode incidence rate ratios.: https://cdn.elifesciences.org/articles/83116/elife-83116-table2-data1-v2.zip
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Table 3

Statistically significant associations between the ABO/RhD blood groups and the age of the first diagnosis.

			Blood group A		Blood group B		Blood group AB		Blood group 0		Blood group RhD
Phecode	Phenotype	N	Estimate (95% CI)	p-value	Estimate (95% CI)	p-value	Estimate (95% CI)	p-value	Estimate (95% CI)	p-value	Estimate (95% CI)	p-value
079	Viral infection	25075	–0.26 (–3.06, 2.54)	0.864	0.92 (0.13, 1.71)	0.022	0.53 (–6.18, 7.23)	0.887	–0.23 (–3.22, 2.75)	0.887	0.27 (–5.22, 5.75)	0.93
451	Phlebitis and thrombophlebitis	16748	–0.58 (–1.02,–0.13)	0.011	–0.24 (–5.71, 5.22)	0.936	–0.6 (–5.87, 4.66)	0.833	0.91 (0.57, 1.25)	<0.001	0.01 (–0.33, 0.34)	0.97
451.2	Phlebitis and thrombophlebitis of lower extremities	15650	–0.53 (–1.08, 0.01)	0.055	–0.27 (–5.85, 5.31)	0.93	–0.7 (–6.35, 4.95)	0.82	0.9 (0.55, 1.25)	<0.001	0.08 (–3.89, 4.06)	0.97
474	Acute and chronic tonsillitis	41428	–0.29 (–1.45, 0.87)	0.634	0.42 (–1.97, 2.8)	0.744	0.38 (–5.71, 6.48)	0.909	0.05 (–2.15, 2.24)	0.97	0.67 (0.15, 1.19)	0.011
474.1	Acute tonsillitis	18162	0.1 (–4.42, 4.61)	0.97	0.41 (–7.17, 7.98)	0.923	0.75 (–7.23, 8.74)	0.864	–0.42 (–3.76, 2.93)	0.82	1.34 (0.64, 2.04)	<0.001

a. Statistically significant effect estimates are marked with bold (FDR adjusted P-value <0.05).
b. FDR adjusted p-values and 95% confidence intervals are presented.
c. FDR adjusted p-values above 0.97 were set to 0.97 to enable estimation of adjusted confidence intervals.
d. Estimates represent increases or decreases in years of age of first diagnosis.

Table 3—source data 1 Associations between the ABO/RhD blood groups and the age of the first diagnosis.: https://cdn.elifesciences.org/articles/83116/elife-83116-table3-data1-v2.zip
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Additional files

Supplementary file 1 Population at the first day of the quarter by region and country of origin.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp1-v2.docx
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Supplementary file 2 List of Phecodes defined as congenital or hereditary.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp2-v2.docx
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Supplementary file 3 The study sample birth year distribution.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp3-v2.docx
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Supplementary file 4

Associations between the ABO/RhD blood groups and Phecode incidence rate ratios of all analyzed Phecodes.

a. Statistically significant IRRs are marked with bold (FDR adjusted P-value <0.05). b. The IRRs are adjusted for age, sex, interaction between age and sex, and birth year. c. All other ABO blood groups and the RhD negative blood group was used as a reference, respectively. d. The FDR adjusted p-values and 95% confidence intervals are presented. e. FDR adjusted p-values above 0.97 were set to 0.97 to avoid exploding adjusted confidence intervals. e. Phecodes are divided by PheWAS disease categories. f. The number of events and the follow-up time in person-years for each Phecode is also presented. g. For study results of congenital Phecodes estimates marked with ** are prevalence ratios instead of IRRs and the corresponding person-year marked with * are the size of the cohort.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp4-v2.docx
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Supplementary file 5 Associations between ABO/RhD blood groups and the age of the first diagnosis. a. Statistically significant effect estimates are marked with bold (FDR adjusted P-value <0.05). b. The FDR adjusted p-values and 95% confidence intervals are presented. c. FDR adjusted p-values above 0.97 were set to 0.97 to enable estimation of adjusted confidence intervals. d. Estimates represent increases or decreases in years of age of first diagnosis.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp5-v2.docx
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Supplementary file 6

Statistically significant associations for blood groups A, B and AB relative to blood group O. Further, also for RhD positive blood group relative to the RhD negative blood group.

a. Statistically significant IRRs are marked with bold (FDR adjusted P-value <0.05). b. The IRRs are adjusted for age, sex, interaction between age and sex, and birth year. c. Blood group O and the RhD negative blood group was used as a reference, respectively. d. The FDR adjusted p-values and 95% confidence intervals are presented. e. FDR adjusted p-values above 0.97 were set to 0.97 to avoid exploding adjusted confidence intervals. f. Phecodes are divided by PheWAS disease categories. g. The number of events and the follow-up time in person-years for each Phecode is also presented. h. For study results of congenital Phecodes estimates marked with ** are prevalence ratios instead of IRRs and the corresponding person-year marked with * are the size of the cohort.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp6-v2.docx
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Supplementary file 7

Associations between the ABO/RhD blood groups and Phecode incidence rate ratios of all analyzed Phecodes with blood group O and RhD negative as the reference, respectively.

a. Statistically significant IRRs are marked with bold (FDR adjusted P-value <0.05). b. The IRRs are adjusted for age, sex, interaction between age and sex, and birth year. c. Blood group O and the RhD negative blood group was used as a reference, respectively. d. The FDR adjusted p-values and 95% confidence intervals are presented. e. FDR adjusted p-values above 0.97 were set to 0.97 to avoid exploding adjusted confidence intervals. f. Phecodes are divided by PheWAS disease categories. g. The number of events and the follow-up time in person-years for each Phecode is also presented. h. For study results of congenital Phecodes estimates marked with ** are prevalence ratios instead of IRRs and the corresponding person-year marked with * are the size of the cohort.: https://cdn.elifesciences.org/articles/83116/elife-83116-supp7-v2.docx
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MDAR checklist: https://cdn.elifesciences.org/articles/83116/elife-83116-mdarchecklist1-v2.pdf
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