Reduced smoking attenuates the effect of genetic predisposition on premature ovarian aging: a large population-based longitudinal study

Genetic factors play an important role in premature ovarian aging, and smoking is the modifiable factor most reproducibly linked to ovarian aging. We aimed to explore whether and to what extent reduced smoking can mitigate the risk of ovarian aging related to genetic factors. This study was based on data from the UK Biobank recruited 500,000 participants. We identified cases of premature ovarian aging as women who reported natural menopause before the age of 45 years. Genetic susceptibility to premature ovarian aging was estimated by polygenic risk scores and further categorized into high, intermediate, and low genetic risk categories. The measurement of a person's exposure to tobacco is pack-year which is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. Data were analyzed using logistic regression models. The odd ratio (OR) of premature ovarian aging in women with a high genetic risk but never smoking (OR=2.75, 95%CI 2.59–2.92) was reduced nearly by half, compared with those with a high genetic risk and 30 pack-years of smoking (OR=4.42, 95%CI 4.02–4.85). Similar patterns were also observed in other genetic risk categories.Tabled 1Table 1. Risk of premature ovarian aging according to pack-years of smoking within each genetic risk categoryGenetic riskPrevalenceAdjusted model(No. of cases / Total No. of Participants)OR95% CIP valueLow genetic riskNever smoking7.4% (1814/24676)RefRefRef<10 pack-years7.8% (261/3361)1.010.87, 1.160.88810-20 pack-years9.9% (313/3168)1.301.14, 1.49<0.00120-30 pack-years10.9% (250/2296)1.351.16, 1.57<0.001>=30 pack-years12.6% (380/3012)1.531.34, 1.74<0.001Intermediate genetic riskNever smoking11.6% (3026/26107)1.601.50, 1.71<0.001<10 pack-years11.2% (403/3598)1.561.38, 1.76<0.00110-20 pack-years15.2% (542/3569)2.011.80, 2.24<0.00120-30 pack-years17.9% (448/2509)2.412.14, 2.72<0.001>=30 pack-years19.5% (626/3216)2.532.26, 2.82<0.001High genetic riskNever smoking18.7% (4998/26725)2.752.59, 2.92<0.001<10 pack-years20.3% (749/3685)2.992.70, 3.30<0.00110-20 pack-years24.5% (912/3728)3.703.36, 4.06<0.00120-30 pack-years27.6% (719/2602)4.073.66, 4.53<0.001>=30 pack-years29.1% (1020/3507)4.424.02, 4.85<0.001 Open table in a new tab Adherence to non-smoking may attenuate the risk of premature ovarian aging nearly by half across entire populations, even in those with high genetic risk.