When the aMCI patients were divided into...

When the aMCI patients were divided into the low and high PRS_sMDD groups, the high PRS_sMDD group (65.38%) showed 16.25% higher conversion rate than the low PRS_sMDD group (49.13%) (P = 0.002). When patients were divided into the double low risk group, low PRS_sAD but high PRS_sMDD group, high PRS_sAD but low PRS_sMDD group, and double high risk group. There were significant differences in the conversion rate of the aMCI among these hierarchical PRS groups (P = 4.26 × 10⁻⁷). In the low PRS_sAD group, the aMCI patients with high PRS_sMDD showed marginally higher conversion rate than those with low PRS_sMDD (36.84% versus 51.81%, P = 0.05). In the high PRS_sAD group, the aMCI patients with high PRS_sMDD showed significantly higher conversion rate than those with low PRS_sMDD (63.21% versus 80.26%, P = 0.002) (Fig. 2I and Table 3). When PRS_sMDD and PRS_sAD were trisected into the low, middle and high risk, there were significant differences in conversion rate among the nine hierarchical PRS groups (P = 3.23 × 10⁻⁶) (Supplementary materials andSupplementary Table 6).

Table 3

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Conversion rates of aMCI in the bisected PRS groups

PRS groups	aMCI-S, n	aMCI-C, n	Conversion rate, %
Low PRS_sAD and low PRS_sMDD	48	28	36.84
Low PRS_sAD and high PRS_sMDD	40	43	51.81
High PRS_sAD and low PRS_sMDD	32	55	63.21
High PRS_sAD and high PRS_sMDD	15	61	80.26
All	135	187	58.07

PRS groups	aMCI-S, n	aMCI-C, n	Conversion rate, %
Low PRS_sAD and low PRS_sMDD	48	28	36.84
Low PRS_sAD and high PRS_sMDD	40	43	51.81
High PRS_sAD and low PRS_sMDD	32	55	63.21
High PRS_sAD and high PRS_sMDD	15	61	80.26
All	135	187	58.07

Table 3

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Conversion rates of aMCI in the bisected PRS groups

PRS groups	aMCI-S, n	aMCI-C, n	Conversion rate, %
Low PRS_sAD and low PRS_sMDD	48	28	36.84
Low PRS_sAD and high PRS_sMDD	40	43	51.81
High PRS_sAD and low PRS_sMDD	32	55	63.21
High PRS_sAD and high PRS_sMDD	15	61	80.26
All	135	187	58.07

PRS groups	aMCI-S, n	aMCI-C, n	Conversion rate, %
Low PRS_sAD and low PRS_sMDD	48	28	36.84
Low PRS_sAD and high PRS_sMDD	40	43	51.81
High PRS_sAD and low PRS_sMDD	32	55	63.21
High PRS_sAD and high PRS_sMDD	15	61	80.26
All	135	187	58.07

Table 4

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Top 10 neighbouring genes of the PPI network from PRS_sMDD fine-mapping of 1860 genes and PRS_sMDD fine-mapping of 1608 genes

Ranking	PRS_sMDD fine-mapping of 1860 genes^a		PRS_sMDD fine-mapping of 1608 genes^b
Ranking	Gene symbol	Random walk probability	Gene symbol	Random walk probability
1	APP	6.84 × 10⁻³	APP	6.78 × 10⁻³
2	ELAVL1	4.49 × 10⁻³	ELAVL1	4.49 × 10⁻³
3	NTRK1	2.21 × 10⁻³	NXF1	2.25 × 10⁻³
4	NXF1	2.03 × 10⁻³	NTRK1	2.17 × 10⁻³
5	CUL3	1.70 × 10⁻³	CUL3	1.71 × 10⁻³
6	MOV10	1.50 × 10⁻³	MOV10	1.50 × 10⁻³
7	TP53	1.45 × 10⁻³	UBC	1.46 × 10⁻³
8	EWSR1	1.43 × 10⁻³	TR53	1.32 × 10⁻³
9	UBC	1.42 × 10⁻³	EWSR1	1.19 × 10⁻³
10	TMEM17	1.33 × 10⁻³	COPS5	1.17 × 10⁻³

Ranking	PRS_sMDD fine-mapping of 1860 genes^a		PRS_sMDD fine-mapping of 1608 genes^b
Ranking	Gene symbol	Random walk probability	Gene symbol	Random walk probability
1	APP	6.84 × 10⁻³	APP	6.78 × 10⁻³
2	ELAVL1	4.49 × 10⁻³	ELAVL1	4.49 × 10⁻³
3	NTRK1	2.21 × 10⁻³	NXF1	2.25 × 10⁻³
4	NXF1	2.03 × 10⁻³	NTRK1	2.17 × 10⁻³
5	CUL3	1.70 × 10⁻³	CUL3	1.71 × 10⁻³
6	MOV10	1.50 × 10⁻³	MOV10	1.50 × 10⁻³
7	TP53	1.45 × 10⁻³	UBC	1.46 × 10⁻³
8	EWSR1	1.43 × 10⁻³	TR53	1.32 × 10⁻³
9	UBC	1.42 × 10⁻³	EWSR1	1.19 × 10⁻³
10	TMEM17	1.33 × 10⁻³	COPS5	1.17 × 10⁻³

^aPRS_sMDD genetic variants were fine-mapped into 1860 genes based on the hippocampal-specific regulatory probability between eQTLs and epigenomic features (within a 5-kb window).

^bPRS_sMDD genetic variants were fine-mapped into 1608 genes based on physical position of each variant (within a 5-kb window).

The abbreviation of genes is referred to at https://www.ncbi.nlm.nih.gov/gene/.

Table 4

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Top 10 neighbouring genes of the PPI network from PRS_sMDD fine-mapping of 1860 genes and PRS_sMDD fine-mapping of 1608 genes

Ranking	PRS_sMDD fine-mapping of 1860 genes^a		PRS_sMDD fine-mapping of 1608 genes^b
Ranking	Gene symbol	Random walk probability	Gene symbol	Random walk probability
1	APP	6.84 × 10⁻³	APP	6.78 × 10⁻³
2	ELAVL1	4.49 × 10⁻³	ELAVL1	4.49 × 10⁻³
3	NTRK1	2.21 × 10⁻³	NXF1	2.25 × 10⁻³
4	NXF1	2.03 × 10⁻³	NTRK1	2.17 × 10⁻³
5	CUL3	1.70 × 10⁻³	CUL3	1.71 × 10⁻³
6	MOV10	1.50 × 10⁻³	MOV10	1.50 × 10⁻³
7	TP53	1.45 × 10⁻³	UBC	1.46 × 10⁻³
8	EWSR1	1.43 × 10⁻³	TR53	1.32 × 10⁻³
9	UBC	1.42 × 10⁻³	EWSR1	1.19 × 10⁻³
10	TMEM17	1.33 × 10⁻³	COPS5	1.17 × 10⁻³

Ranking	PRS_sMDD fine-mapping of 1860 genes^a		PRS_sMDD fine-mapping of 1608 genes^b
Ranking	Gene symbol	Random walk probability	Gene symbol	Random walk probability
1	APP	6.84 × 10⁻³	APP	6.78 × 10⁻³
2	ELAVL1	4.49 × 10⁻³	ELAVL1	4.49 × 10⁻³
3	NTRK1	2.21 × 10⁻³	NXF1	2.25 × 10⁻³
4	NXF1	2.03 × 10⁻³	NTRK1	2.17 × 10⁻³
5	CUL3	1.70 × 10⁻³	CUL3	1.71 × 10⁻³
6	MOV10	1.50 × 10⁻³	MOV10	1.50 × 10⁻³
7	TP53	1.45 × 10⁻³	UBC	1.46 × 10⁻³
8	EWSR1	1.43 × 10⁻³	TR53	1.32 × 10⁻³
9	UBC	1.42 × 10⁻³	EWSR1	1.19 × 10⁻³
10	TMEM17	1.33 × 10⁻³	COPS5	1.17 × 10⁻³

^aPRS_sMDD genetic variants were fine-mapped into 1860 genes based on the hippocampal-specific regulatory probability between eQTLs and epigenomic features (within a 5-kb window).

^bPRS_sMDD genetic variants were fine-mapped into 1608 genes based on physical position of each variant (within a 5-kb window).

The abbreviation of genes is referred to at https://www.ncbi.nlm.nih.gov/gene/.

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