Table 4.

Additive interaction between polygenic risk score and body mass index in male and female participants

		BMI < 25 kg/m2	BMI ≥ 25 kg/m2	Interaction P-value
All participants (HPFS, NHS and NHS II)
PRSa < 0	Cases/Controls	723/3891	1554/4059
	ORb (95% CI)	1.0Ref	2.13 (2.02, 2.24)
PRSa ≥ 0	Cases/Controls	826/3144	1682/3252
	ORb (95% CI)	1.42 (1.32, 1.52)	2.90 (2.76, 3.04)
Combined Association
Additive interaction: RERI for (95% Cl); H0c: RERI = 0			0.35 (0.11, 0.60)	4.85×10−3
Additive interaction: SI (95% CI); H0c: SI = 1			1.23 (1.07, 1.38)	8.59×10−3
Multiplicative interaction: IOR (95% CI); H0c: IOR = 1			0.96 (0.82, 1.10)	5.70×10−1
Among females (NHS and NHS II)
PRSa < 0	Cases/Controls	586/3283	1252/3197
	ORb (95% CI)	1.0Ref	2.29 (2.17, 2.41)
PRSa ≥ 0	Cases/Controls	681/2630	1369/2545
	ORb (95% CI)	1.45 (1.34, 1.56)	3.15 (3.00, 3.30)
Combined Association
Additive interaction: RERI for (95% Cl); H0c: RERI = 0			0.41 (0.12, 0.70)	5.61×10−3
Additive interaction: SI (95% CI); H0c: SI = 1			1.24 (1.08, 1.39)	9.34×10−3
Multiplicative interaction: IOR (95% CI); H0c: IOR = 1			0.95 (0.80, 1.10)	4.97×10−1
Among males (HPFS)
PRSa < 0	Cases/Controls	137/608	302/862
	ORb (95% CI)	1.0Ref	1.56 (1.30, 1.82)
PRSa ≥ 0	Cases/Controls	145/514	313/707
	ORb (95% CI)	1.25 (1.03, 1.48)	2.01 (1.69, 2.33)
Combined Association
Additive interaction: RERI for (95% Cl); H0c: RERI = 0			0.20 (−0.24, 0.64)	3.77×10−1
Additive interaction: SI (95% CI); H0c: SI = 1			1.24 (0.70, 1.78)	4.30×10−1
Multiplicative interaction: IOR (95% CI); H0c: IOR = 1			1.03 (0.71, 1.35)	8.64×10−1

^aPRS < 0 refers to PRS below the mean. PRS ≥ 0 refers to PRS above or equal to the mean.

^bOdds ratios are unadjusted and conditional on matching factors.

^cH0 = the null hypotheses tests were for RERI = 0; Synergy Index = 1 and interaction odds ratio = 1