Table 2:

Assessment of previously implicated variants in APOE. These variants were directly genotyped by qPCR given their previously implicated role in disease. β is the effect in years on age at dementia onset (i.e., positive β values indicate an association with later age of onset). One other APOE coding variant, rs440446–G, was imputed by TOPMed but did not exhibit a meaningful signal (β= −0.57, p=0.16, see Supplemental Table 2 for details). TOPMed Bravo Freeze 8 was used for Population Allele Frequency.

Variant–Effect Allele	Description	β (SE)	p	# Homozygous	Cohort Allele Frequency	Population Allele Frequency	Transcript ENST00000252486.9 Coding Change	CADD version 1.6
rs429358–C	APOE ε4 (when rs7412 ref.)	−2.0 (0.6)	0.0025	8	0.138	0.155	p.(Cys130Arg)	16.7
rs121918393–A	APOE Christchurch	3.1 (1.6)	0.0496	1	0.020	1.9x10−5	p.(Arg154Ser)	25.3
rs7412–T	APOE ε2 (when rs429358 ref.)	2.0 (0.9)	0.0891	0	0.068	0.078	p.(Arg176Cys)	26