A total of 394,053 participants aged 38–73 years (204,194 females, 189,859 males) were given a constructed lifestyle score (4.80 ± 1.35) at baseline, of which 1.15% were classified into an unfavourable lifestyle category (scoring 0–1), 37.53% were categorized as intermediate lifestyle (scoring 2–4) and 61.32% following a favourable lifestyle (scoring 5–7). Participants classified as healthy in each lifestyle factor generally exhibited higher socioeconomic status and education levels, and as the composite lifestyle class increased, socioeconomic status and education level also improved. (Table 1). We further select participants to include those with linkage to the diagnostic outcomes of 45 diseases. Over a median follow-up period ranging from 13.60 to 13.84 years, we identified a total of 285,681 to 394,038 participants with associations with the corresponding diagnostic records, of whom 108 to 47,695 individuals experienced the onset of a specific disease. Demographic characteristics of participants were provided in Supplementary Tables 4–49.
Multivariable Cox proportional hazard regression models were employed to examine the association of combined lifestyle with all incident diseases. The results consistently showed that when low-risk lifestyle factors were considered jointly, the risk of all diseases decreased monotonically. Compared with an unfavourable lifestyle, a favourable lifestyle was associated with a significant lower risk in the majority of diseases (41 diseases, representing 91% of those examined) after False discovery rate (FDR) correction, except for amyotrophic lateral sclerosis (ALS), ulcerative colitis (UC), prostate disorder (PROST), and breast cancer (Supplementary Table 51). In terms of the 8 disease categories, adherence to a favourable lifestyle contributed the most to a protective impact on the risk of respiratory diseases (HRs across this disease category: 0.10–0.59), brain disorders (0.23–0.69), cancer (0.18–0.84) and digestive diseases (0.17–0.83). The protective effect was relatively smaller for autoimmune disease (0.44–0.68), cardiovascular disease (0.41–0.66), endocrine disease (0.42–0.69), and genitourinary system disease (0.44–0.98).
For respiratory system diseases, representative of lung disease, a favourable lifestyle reduced the risk of emphysema (EMP) by 90% (HR: 0.10, 95% CI: 0.09–0.12) and lung cancer by 82% (0.18, 0.14–0.21). For digestive disease, especially liver-related diseases, a favourable lifestyle reduced the risk of chronic liver disease (CLD) by 83% (0.17, 0.14–0.20) and liver cancer by 76% (0.24, 0.14–0.40). For brain disorders, a favourable lifestyle exerted a significant protective impact on both psychiatric disorders and chronic nervous system diseases. Specifically, the adjusted HR for psychiatric disorders such as schizophrenia (SCZ) was 0.24 (95% CI, 0.14–0.40), bipolar disorder (BP) was 0.29 (0.19–0.46), and MDD was 0.31 (0.28–0.33). Moreover, chronic nervous system diseases, including multiple sclerosis (MS), displayed an adjusted HR of 0.29 (0.15–0.56), while epilepsy (EPI) exhibited a ratio of 0.40 (0.31–0.52). Full results are shown in Fig. 1A, 2 and Supplementary Table 51. When considering the composited lifestyle scores as a continuous variable, the most significant protective effect was noted for EMP. Specifically, the HR for participants with lifestyle scores of 1, 2, 3, 4, 5, 6, and 7 compared to those with a score of 0 were 0.69 (0.49–0.97), 0.48 (0.34–0.66), 0.27 (0.20–0.38), 0.18 (0.13–0.25), 0.10 (0.07–0.14), 0.05 (0.04–0.07), 0.02 (0.01–0.03), respectively (Supplementary Table 52). When treated as a quantitative variable, each 1-point increment in the healthy lifestyle score was associated with a HR for EMP of 0.59 (95% CI, 0.58–0.60).
We further examined the specific protective effects of individual lifestyle factors on these three categories of diseases (Fig. 1B). For lung-related respiratory diseases, never smoking demonstrated the most prominent protective influence against the risk of EMP (HR: 0.13, 95% CI: 0.12–0.15), lung cancer (0.17, 0.15–0.19), pneumonia (PNEU) (0.67, 0.65–0.69), and bronchitis (BRON) (0.77, 0.71–0.82). Regarding liver-related disease, moderate alcohol consumption emerged as the most significant factor with significant risk reduction, associated with a lower risk of CLD by 64% (0.36, 0.34–0.39) and liver cancer by 48% (0.52, 0.42–0.63). As for brain disorders, optimal sleep pattern and frequent social connection demonstrated the most pronounced protective effect against the risk of major psychiatric disorders. Optimal sleep pattern was associated with a 45% reduction in anorexia nervosa (EAT) (0.55, 0.37–0.82), a 29% reduction in SCZ (0.71, 0.62–0.82), a 28% reduction in MDD (0.72, 0.70–0.75), and a 23% reduction in ANX (0.77, 0.75–0.80). Comparably, frequent social connections entailed a 55% risk reduction in obsessive-compulsive disorder (OCD) (0.45, 0.34–0.61), a 44% reduction in SCZ (0.56, 0.48–0.65), and a 31% reduction in BP (0.69, 0.56–0.84). For chronic nervous system diseases, regular physical activity was associated with a 41% lower risk of MS (0.59, 0.47–0.74). Moderate alcohol consumption also significantly reduced the risk of EPI by 24% (0.76, 0.70–0.83) and Alzheimer’s disease (AD) by 16% (0.84, 0.77–0.90). Full results of the prospective effects of individual lifestyle factors on all diseases were listed in Supplementary Table 50.
When combining the genetic risk and lifestyle scores, with participants with high genetic risk and unfavourable lifestyle as the reference group, those with low genetic risk and favourable lifestyle had a substantially lower risk of brain disorders, involving a 92% reduction in the risk of AD (HR, 0.08, [95%CI, 0.05–0.12]) and a 74% reduction in MDD (0.26, 0.21–0.32). Respiratory disease also displayed significant risk reduction in the context of combining low genetic risk and favourable lifestyle, with a 92% risk reduction of COPD (consist of the two subtypes of EMP and PNEU) (0.08, 0.07–0.10) and 70% risk reduction of asthma (ASM) (0.30, 0.24–0.39). No significant interaction was observed between PRS and lifestyle score in these two categories of diseases. This suggested that lifestyle plays a robust protective role across various genetic profiles. However, significant interactions between PRS and lifestyle was observed in 4 cardiovascular diseases (atrial fibrillation (AF, FDR corrected P value for interaction = 4.75\(\times\)10−3), HF (FDR corrected P value for interaction = 3.18\(\times\)10−3), hypertension (HTN, FDR corrected P value for interaction = 1.74\(\times\)10−3), venous thromboembolism (VIE, FDR corrected P value for interaction = 3.18\(\times\)10−3)), and 2 endocrine diseases (obesity (OBS, FDR corrected P value for interaction = 3.52\(\times\)10−6) and osteoporosis (OST, FDR corrected P value for interaction = 3.65\(\times\)10−5)), in which participants with low genetic risk and favourable lifestyle decreased the risk from 18–57%, thereby confirming the protective role of favourable lifestyle on these diseases (Table 2).
Table 2
Combining effect of genetic risk and lifestyle on the full spectrum of diseases
Brain disorders
|
Lifestyle class
|
PRS Level
|
Number of Cases/Total
|
HR [95%CI]
|
P value
|
P for interaction (FDR corrected)
|
AD
|
|
|
|
|
0.18
|
Unfavourable
|
High PRS
|
27 / 1032
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
699 / 35465
|
0.56(0.38,0.83)
|
3.70\(\times\)10−3
|
|
Unfavourable
|
Low PRS
|
1020 / 59371
|
0.53(0.36,0.78)
|
1.31\(\times\)10−3
|
|
Intermediate
|
High PRS
|
15 / 2211
|
0.22(0.12,0.41)
|
2.60\(\times\)10−6
|
|
Intermediate
|
Intermediate PRS
|
447 / 72459
|
0.17(0.11,0.25)
|
4.17\(\times\)10−19
|
|
Intermediate
|
Low PRS
|
569 / 117693
|
0.15(0.10,0.21)
|
2.31\(\times\)10−22
|
|
Favourable
|
High PRS
|
7 / 1108
|
0.21(0.09,0.47)
|
1.99\(\times\)10−4
|
|
Favourable
|
Intermediate PRS
|
133 / 36213
|
0.10(0.07,0.15)
|
2.56\(\times\)10−27
|
|
Favourable
|
Low PRS
|
164 / 58654
|
0.08(0.05,0.12)
|
9.34\(\times\)10−33
|
|
ANX
|
|
|
|
|
0.99
|
Unfavourable
|
High PRS
|
65 / 796
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1471 / 28523
|
0.61(0.48,0.79)
|
1.15\(\times\)10−4
|
|
Unfavourable
|
Low PRS
|
1772 / 47565
|
0.45(0.35,0.57)
|
2.19\(\times\)10−10
|
|
Intermediate
|
High PRS
|
179 / 1703
|
1.30(0.98,1.73)
|
0.07
|
|
Intermediate
|
Intermediate PRS
|
3159 / 57618
|
0.66(0.52,0.85)
|
1.07\(\times\)10−3
|
|
Intermediate
|
Low PRS
|
3872 / 96059
|
0.49(0.38,0.63)
|
1.42\(\times\)10−8
|
|
Favourable
|
High PRS
|
87 / 899
|
1.20(0.87,1.66)
|
0.26
|
|
Favourable
|
Intermediate PRS
|
1724 / 28761
|
0.72(0.56,0.93)
|
0.01
|
|
Favourable
|
Low PRS
|
2070 / 47504
|
0.53(0.41,0.68)
|
5.16\(\times\)10−7
|
|
MDD
|
|
|
|
|
0.06
|
Unfavourable
|
High PRS
|
99 / 858
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1634 / 27965
|
0.52(0.42,0.63)
|
1.99\(\times\)10−10
|
|
Unfavourable
|
Low PRS
|
1636 / 42620
|
0.36(0.30,0.44)
|
1.60\(\times\)10−22
|
|
Intermediate
|
High PRS
|
172 / 1451
|
1.05(0.82,1.35)
|
0.69
|
|
Intermediate
|
Intermediate PRS
|
2827 / 54008
|
0.48(0.39,0.58)
|
4.95\(\times\)10−13
|
|
Intermediate
|
Low PRS
|
2974 / 92753
|
0.31(0.25,0.38)
|
5.03\(\times\)10−30
|
|
Favourable
|
High PRS
|
61 / 654
|
0.83(0.61,1.15)
|
0.27
|
|
Favourable
|
Intermediate PRS
|
1205 / 26309
|
0.42(0.34,0.52)
|
1.41\(\times\)10−16
|
|
Favourable
|
Low PRS
|
1315 / 49162
|
0.26(0.21,0.32)
|
1.87\(\times\)10−37
|
|
PD
|
|
|
|
|
0.53
|
Unfavourable
|
High PRS
|
25 / 1006
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
775 / 35016
|
0.85(0.57,1.27)
|
0.43
|
|
Unfavourable
|
Low PRS
|
1003 / 59159
|
0.72(0.49,1.08)
|
0.11
|
|
Intermediate
|
High PRS
|
66 / 2129
|
1.28(0.81,2.03)
|
0.29
|
|
Intermediate
|
Intermediate PRS
|
1287 / 71729
|
0.68(0.46,1.02)
|
0.06
|
|
Intermediate
|
Low PRS
|
1511 / 117451
|
0.55(0.37,0.81)
|
2.89\(\times\)10−3
|
|
Favourable
|
High PRS
|
25 / 1179
|
0.86(0.49,1.49)
|
0.58
|
|
Favourable
|
Intermediate PRS
|
544 / 36273
|
0.57(0.38,0.85)
|
5.72\(\times\)10−3
|
|
Favourable
|
Low PRS
|
651 / 57890
|
0.47(0.32,0.71)
|
2.57\(\times\)10−4
|
|
Respiratory diseases
|
|
|
|
|
|
ASM
|
|
|
|
|
0.39
|
Unfavourable
|
High PRS
|
63 / 922
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1457 / 29768
|
0.75(0.58,0.96)
|
0.02
|
|
Unfavourable
|
Low PRS
|
1667 / 47312
|
0.60(0.46,0.77)
|
6.27\(\times\)10−5
|
|
Intermediate
|
High PRS
|
86 / 1831
|
0.70(0.50,0.96)
|
0.03
|
|
Intermediate
|
Intermediate PRS
|
2202 / 63593
|
0.53(0.41,0.68)
|
7.95\(\times\)10−7
|
|
Intermediate
|
Low PRS
|
2618 / 105854
|
0.42(0.33,0.54)
|
1.45\(\times\)10−11
|
|
Favourable
|
High PRS
|
29 / 886
|
0.47(0.31,0.74)
|
8.88\(\times\)10−4
|
|
Favourable
|
Intermediate PRS
|
883 / 32851
|
0.42(0.32,0.54)
|
1.75\(\times\)10−11
|
|
Favourable
|
Low PRS
|
997 / 56257
|
0.30(0.24,0.39)
|
7.48\(\times\)10−20
|
|
COPD
|
|
|
|
|
0.07
|
Unfavourable
|
High PRS
|
163 / 851
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
2469 / 29116
|
0.45(0.38,0.53)
|
4.13\(\times\)10−23
|
|
Unfavourable
|
Low PRS
|
1379 / 47529
|
0.18(0.16,0.22)
|
7.44\(\times\)10−92
|
|
Intermediate
|
High PRS
|
251 / 1615
|
0.72(0.59,0.88)
|
1.37\(\times\)10−3
|
|
Intermediate
|
Intermediate PRS
|
3399 / 58093
|
0.30(0.25,0.35)
|
2.24\(\times\)10−51
|
|
Intermediate
|
Low PRS
|
1789 / 98551
|
0.11(0.10,0.13)
|
4.63\(\times\)10−154
|
|
Favourable
|
High PRS
|
97 / 794
|
0.57(0.44,0.73)
|
1.05\(\times\)10−5
|
|
Favourable
|
Intermediate PRS
|
1284 / 29420
|
0.22(0.18,0.26)
|
7.27\(\times\)10−75
|
|
Favourable
|
Low PRS
|
665 / 49853
|
0.08(0.07,0.10)
|
5.15\(\times\)10−177
|
|
Cardiovascular diseases
|
|
|
|
|
|
AF
|
|
|
|
|
4.75\(\times\)10−3
|
Unfavourable
|
High PRS
|
164 / 1105
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
4353 / 34982
|
0.82(0.70,0.96)
|
0.01
|
|
Unfavourable
|
Low PRS
|
5392 / 56551
|
0.76(0.65,0.89)
|
6.47\(\times\)10−4
|
|
Intermediate
|
High PRS
|
215 / 2147
|
0.66(0.54,0.81)
|
6.52\(\times\)10−5
|
|
Intermediate
|
Intermediate PRS
|
5351 / 70730
|
0.47(0.40,0.55)
|
4.54\(\times\)10−21
|
|
Intermediate
|
Low PRS
|
6106 / 116487
|
0.40(0.34,0.46)
|
3.80\(\times\)10−31
|
|
Favourable
|
High PRS
|
57 / 998
|
0.36(0.26,0.48)
|
2.22\(\times\)10−11
|
|
Favourable
|
Intermediate PRS
|
1600 / 35293
|
0.28(0.24,0.33)
|
3.92\(\times\)10−55
|
|
Favourable
|
Low PRS
|
1872 / 58917
|
0.24(0.20,0.28)
|
1.42\(\times\)10−69
|
|
CAD
|
|
|
|
|
0.07
|
Unfavourable
|
High PRS
|
188 / 911
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
4480 / 32758
|
0.67(0.57,0.77)
|
4.64\(\times\)10−8
|
|
Unfavourable
|
Low PRS
|
4980 / 53458
|
0.54(0.47,0.62)
|
1.37\(\times\)10−16
|
|
Intermediate
|
High PRS
|
274 / 1962
|
0.64(0.53,0.77)
|
3.02\(\times\)10−6
|
|
Intermediate
|
Intermediate PRS
|
6512 / 67259
|
0.44(0.38,0.51)
|
4.22\(\times\)10−28
|
|
Intermediate
|
Low PRS
|
7236 / 113707
|
0.35(0.31,0.41)
|
1.17\(\times\)10−44
|
|
Favourable
|
High PRS
|
113 / 921
|
0.52(0.41,0.65)
|
2.98\(\times\)10−8
|
|
Favourable
|
Intermediate PRS
|
2400 / 33765
|
0.31(0.27,0.36)
|
1.51\(\times\)10−52
|
|
Favourable
|
Low PRS
|
2589 / 58900
|
0.24(0.20,0.28)
|
6.05\(\times\)10−80
|
|
HF
|
|
|
|
|
3.18\(\times\)10−3
|
Unfavourable
|
High PRS
|
51 / 858
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
882 / 29626
|
0.51(0.39,0.68)
|
3.84\(\times\)10−6
|
|
Unfavourable
|
Low PRS
|
897 / 49862
|
0.40(0.30,0.53)
|
1.39\(\times\)10−10
|
|
Intermediate
|
High PRS
|
120 / 1754
|
1.08(0.78,1.49)
|
0.66
|
|
Intermediate
|
Intermediate PRS
|
2352 / 59610
|
0.65(0.50,0.86)
|
2.77\(\times\)10−3
|
|
Intermediate
|
Low PRS
|
2214 / 99956
|
0.49(0.37,0.64)
|
3.59\(\times\)10−7
|
|
Favourable
|
High PRS
|
139 / 945
|
2.40(1.74,3.31)
|
8.73\(\times\)10−8
|
|
Favourable
|
Intermediate PRS
|
2317 / 30053
|
1.32(1.00,1.74)
|
0.05
|
|
Favourable
|
Low PRS
|
1900 / 47494
|
0.88(0.67,1.17)
|
0.39
|
|
HTN
|
|
|
|
|
1.74\(\times\)10−3
|
Unfavourable
|
High PRS
|
186 / 577
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
5354 / 20516
|
0.77(0.67,0.89)
|
5.16\(\times\)10−4
|
|
Unfavourable
|
Low PRS
|
6909 / 36489
|
0.64(0.56,0.74)
|
3.13\(\times\)10−9
|
|
Intermediate
|
High PRS
|
357 / 1299
|
0.78(0.66,0.94)
|
7.30\(\times\)10−3
|
|
Intermediate
|
Intermediate PRS
|
10489 / 49174
|
0.59(0.51,0.68)
|
7.36\(\times\)10−13
|
|
Intermediate
|
Low PRS
|
12982 / 90388
|
0.46(0.40,0.53)
|
5.06\(\times\)10−26
|
|
Favourable
|
High PRS
|
153 / 699
|
0.59(0.47,0.73)
|
1.00\(\times\)10−6
|
|
Favourable
|
Intermediate PRS
|
4524 / 27635
|
0.43(0.37,0.50)
|
9.63\(\times\)10−30
|
|
Favourable
|
Low PRS
|
5522 / 51812
|
0.33(0.28,0.38)
|
5.78\(\times\)10−51
|
|
ISS
|
|
|
|
|
0.98
|
Unfavourable
|
High PRS
|
78 / 1199
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1387 / 36814
|
0.54(0.43,0.68)
|
1.18\(\times\)10−7
|
|
Unfavourable
|
Low PRS
|
1459 / 55255
|
0.43(0.34,0.54)
|
3.69\(\times\)10−13
|
|
Intermediate
|
High PRS
|
84 / 2044
|
0.61(0.45,0.83)
|
1.52\(\times\)10−3
|
|
Intermediate
|
Intermediate PRS
|
2072 / 70503
|
0.41(0.33,0.52)
|
2.69\(\times\)10−14
|
|
Intermediate
|
Low PRS
|
2286 / 116466
|
0.31(0.25,0.39)
|
1.70\(\times\)10−23
|
|
Favourable
|
High PRS
|
25 / 891
|
0.40(0.26,0.63)
|
8.17\(\times\)10−5
|
|
Favourable
|
Intermediate PRS
|
788 / 33713
|
0.33(0.26,0.42)
|
9.29\(\times\)10−21
|
|
Favourable
|
Low PRS
|
956 / 61334
|
0.25(0.20,0.31)
|
8.17\(\times\)10−32
|
|
VIE
|
|
|
|
|
3.18\(\times\)10−3
|
Unfavourable
|
High PRS
|
49 / 1009
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1729 / 34307
|
1.04(0.79,1.39)
|
0.77
|
|
Unfavourable
|
Low PRS
|
2180 / 56203
|
0.93(0.70,1.23)
|
0.61
|
|
Intermediate
|
High PRS
|
95 / 2092
|
0.89(0.63,1.26)
|
0.50
|
|
Intermediate
|
Intermediate PRS
|
2256 / 69650
|
0.66(0.50,0.87)
|
3.68\(\times\)10−3
|
|
Intermediate
|
Low PRS
|
2739 / 115246
|
0.56(0.42,0.74)
|
6.30\(\times\)10−5
|
|
Favourable
|
High PRS
|
37 / 1027
|
0.75(0.49,1.15)
|
0.19
|
|
Favourable
|
Intermediate PRS
|
798 / 35100
|
0.46(0.35,0.62)
|
1.52\(\times\)10−7
|
|
Favourable
|
Low PRS
|
868 / 58243
|
0.35(0.26,0.47)
|
1.59\(\times\)10−12
|
|
Endocrine diseases
|
|
|
|
|
|
OBS
|
|
|
|
|
3.52\(\times\)10−6
|
Unfavourable
|
High PRS
|
218 / 1064
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
4983 / 35244
|
0.80(0.70,0.92)
|
1.58\(\times\)10−3
|
|
Unfavourable
|
Low PRS
|
4677 / 54334
|
0.72(0.63,0.83)
|
3.75\(\times\)10−6
|
|
Intermediate
|
High PRS
|
292 / 2076
|
0.95(0.80,1.13)
|
0.56
|
|
Intermediate
|
Intermediate PRS
|
6954 / 69525
|
0.85(0.74,0.97)
|
0.02
|
|
Intermediate
|
Low PRS
|
6558 / 116457
|
0.67(0.58,0.77)
|
7.51\(\times\)10−9
|
|
Favourable
|
High PRS
|
91 / 998
|
0.87(0.68,1.11)
|
0.27
|
|
Favourable
|
Intermediate PRS
|
2177 / 34544
|
0.72(0.63,0.83)
|
4.01\(\times\)10−6
|
|
Favourable
|
Low PRS
|
2105 / 60291
|
0.55(0.47,0.63)
|
3.40\(\times\)10−17
|
|
OST
|
|
|
|
|
3.65\(\times\)10−5
|
Unfavourable
|
High PRS
|
64 / 1071
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
1609 / 35004
|
0.58(0.45,0.74)
|
1.67\(\times\)10−5
|
|
Unfavourable
|
Low PRS
|
2441 / 56673
|
0.46(0.36,0.59)
|
1.42\(\times\)10−9
|
|
Intermediate
|
High PRS
|
86 / 2108
|
0.61(0.44,0.84)
|
2.84\(\times\)10−3
|
|
Intermediate
|
Intermediate PRS
|
2358 / 70731
|
0.41(0.32,0.52)
|
1.26\(\times\)10−12
|
|
Intermediate
|
Low PRS
|
3371 / 115688
|
0.30(0.24,0.39)
|
3.79\(\times\)10−21
|
|
Favourable
|
High PRS
|
51 / 1034
|
0.79(0.55,1.14)
|
0.21
|
|
Favourable
|
Intermediate PRS
|
818 / 35279
|
0.28(0.22,0.36)
|
1.58\(\times\)10−22
|
|
Favourable
|
Low PRS
|
1019 / 58320
|
0.18(0.14,0.23)
|
4.67\(\times\)10−40
|
|
T2D
|
|
|
|
|
0.10
|
Unfavourable
|
High PRS
|
259 / 1098
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
5340 / 34054
|
0.74(0.66,0.84)
|
3.80\(\times\)10−6
|
|
Unfavourable
|
Low PRS
|
4585 / 53903
|
0.55(0.48,0.62)
|
1.39\(\times\)10−20
|
|
Intermediate
|
High PRS
|
277 / 2037
|
0.50(0.42,0.59)
|
6.31\(\times\)10−16
|
|
Intermediate
|
Intermediate PRS
|
5566 / 69982
|
0.37(0.33,0.42)
|
5.45\(\times\)10−55
|
|
Intermediate
|
Low PRS
|
4615 / 116391
|
0.26(0.23,0.29)
|
1.30\(\times\)10−97
|
|
Favourable
|
High PRS
|
66 / 931
|
0.29(0.22,0.37)
|
1.04\(\times\)10−19
|
|
Favourable
|
Intermediate PRS
|
1255 / 34752
|
0.18(0.15,0.20)
|
1.18\(\times\)10−141
|
|
Favourable
|
Low PRS
|
1079 / 61201
|
0.13(0.11,0.14)
|
4.23\(\times\)10−195
|
|
Autoimmune diseases
|
|
|
|
|
|
RA
|
|
|
|
|
0.18
|
Unfavourable
|
High PRS
|
24 / 1091
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
725 / 35478
|
0.90(0.60,1.36)
|
0.62
|
|
Unfavourable
|
Low PRS
|
778 / 57408
|
0.65(0.44,0.98)
|
0.04
|
|
Intermediate
|
High PRS
|
51 / 2101
|
1.08(0.67,1.76)
|
0.75
|
|
Intermediate
|
Intermediate PRS
|
1020 / 70891
|
0.63(0.42,0.95)
|
0.03
|
|
Intermediate
|
Low PRS
|
1093 / 117086
|
0.45(0.30,0.67)
|
1.08\(\times\)10−4
|
|
Favourable
|
High PRS
|
24 / 1049
|
1.00(0.57,1.76)
|
1.00
|
|
Favourable
|
Intermediate PRS
|
391 / 35427
|
0.49(0.32,0.73)
|
6.03\(\times\)10−4
|
|
Favourable
|
Low PRS
|
405 / 58855
|
0.33(0.22,0.50)
|
1.85\(\times\)10−7
|
|
Cancer
|
|
|
|
|
|
Breast cancer
|
|
|
|
|
0.78
|
Unfavourable
|
High PRS
|
15 / 1144
|
[Reference]
|
/
|
|
Unfavourable
|
Intermediate PRS
|
556 / 36096
|
0.86(0.52,1.44)
|
0.57
|
|
Unfavourable
|
Low PRS
|
1038 / 57559
|
0.77(0.46,1.29)
|
0.32
|
|
Intermediate
|
High PRS
|
20 / 2105
|
0.68(0.35,1.33)
|
0.26
|
|
Intermediate
|
Intermediate PRS
|
1033 / 71115
|
0.80(0.48,1.33)
|
0.39
|
|
Intermediate
|
Low PRS
|
2045 / 115959
|
0.76(0.46,1.26)
|
0.29
|
|
Favourable
|
High PRS
|
18 / 1045
|
1.25(0.63,2.47)
|
0.53
|
|
Favourable
|
Intermediate PRS
|
498 / 34926
|
0.78(0.46,1.30)
|
0.34
|
|
Favourable
|
Low PRS
|
1001 / 58650
|
0.73(0.44,1.22)
|
0.24
|
|
Note: The results of the combined effects of genetic risk and lifestyle classes on the 17 diseases were listed in Supplementary table 54. We utilized the corresponding samples with available lifestyle assessments linkage to diagnostic records and PRS risk scores in the survival analyses. All models were adjusted for age, gender, Townsend deprivation index, BMI and education levels. Two-sided unadjusted association P values from multivariate cox models are given. |
Abbreviation: AD: Alzheimer's disease; PD: Parkinson’s disease; ANX: Anxiety disorder; MDD: Major depression disorder; CAD: Coronary artery disease; ISS: Ischaemic stroke; HTN: Hypertension; VIE: Venous thromboembolism; HF: Heart failure; AF: Atrial fibrillation; T2D: Type 2 diabetes mellitus; OST: Osteoporosis; ASM: Asthma; COPD: Chronic Obstructive Pulmonary Disease; RA: Rheumatoid arthritis; OBS: Obesity. |
Stratified analyses were conducted to explore how socio-demographic factors modify the association between lifestyle and all incident diseases. There were significant interactions observed for 22 diseases in the age subcategory (See Supplementary Table 53), all indicating that a favourable lifestyle reduced more risk in the midlife subgroup (HRs range from 0.07–0.62) than elderly subgroup (HRs range from 0.14–0.93). Gender-stratified analysis revealed significant interaction effects in 14 diseases, but the trends of risk reduction were inconsistent among subgroups of men and women in different diseases. This makes sense when considering that, for example, prostate cancer occurs predominantly in men, whereas breast cancer occurs more frequently in women. Among the 13 diseases with a significant socioeconomic status interaction effect, the influence of lifestyle categories reduced the risk for most of diseases with an increasing quantile of the Townsend Deprivation Index levels. This indicates that with increasing deprivation is associated with increased risk of developing certain forms of disease. In terms of education level, we observed significant interaction effects only in OBS (FDR corrected P value for interaction = 0.01) and T2D (FDR corrected P value for interaction = 1.61 \(\times\) 10− 3). In the case of OBS, the group with lower education levels exhibited a greater risk reduction compared to higher education level group, whereas the effect was reversed in T2D. Full results of stratified analyses were listed in Supplementary table 53.