Children with higher genetic risk for PCOS more likely to develop obesity
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Key takeaways:
- Each 1 standard deviation increase in PCOS polygenic risk score for children and adolescents increases the odds for developing obesity.
- Higher PCOS polygenic risk score is linked to younger age at pubarche.
Children and adolescents with a high polygenic risk score for polycystic ovary syndrome tend to have a higher BMI and are more likely to develop obesity, according to study data.
“The results of our study show that the effects of genetic risk factors for PCOS can manifest in childhood in both boys and girls, at ages well before the typical age range for gonadarche and adrenarche,” Jia Zhu, MD, attending physician in the division of endocrinology at Boston Children’s Hospital and an instructor in pediatrics at Harvard Medical School, told Healio. “Thus, our findings provide evidence that these genetic risk factors can act independently of active ovarian and adrenal androgen function. Characterizing the early consequences of genetic risk for PCOS is the initial step in the future identification of the biological pathways that are altered in PCOS.”
Researchers collected genotype data from four cohorts of children and adolescents: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Project Viva and the Holbaek Study. Children aged 2.5 to younger than 6.5 years were considered to be in early childhood, mid-childhood included children aged 6.5 to younger than 11.5 years, early adolescence included children aged 11.5 to younger than 16 years and late adolescence included those aged 16 to 20 years. BMI z scores for age and sex were calculated, and youths had obesity if they had a BMI in the 95th percentile or higher. Fat and lean mass were measured through DXA scans. Lipids were obtained through blood samples. The PCOS polygenic risk score was calculated using summary statistics from a genome-wide association study meta-analysis for PCOS.
The findings were published in The Journal of Clinical Endocrinology & Metabolism.
PCOS polygenic risk score linked to higher BMI, obesity odds
Each 1 standard deviation increase in PCOS polygenic risk score was associated with a higher BMI z score during mid-childhood (beta = 0.05; 95% CI, 0.03-0.07), early adolescence (beta = 0.07; 95% CI, 0.04-0.1) and late adolescence (beta = 0.04; 95% CI, 0.01-0.08) Each 1 standard deviation increase in PCOS polygenic risk score was also associated with increased odds for obesity in early childhood (OR = 1.34; 95% CI, 1.13-1.59), mid-childhood (OR = 1.18; 95% CI, 1.1-1.28), early adolescence (OR = 1.11; 95% CI, 1.03-1.21) and late adolescence (OR = 1.1; 95% CI, 1.01-1.21).
A higher polygenic risk score was associated with increases in fat mass index in all four age groups. Each 1 standard deviation increase in PCOS polygenic risk score was linked to a 0.05 kg/m2 increase in lean mass index during early adolescence, but no associations were observed in the other age groups. PCOS polygenic risk score was not associated with cholesterol, triglycerides or insulin resistance.
The associations between PCOS polygenic risk score and BMI z score, obesity and fat mass index were similar for boys and girls in mid-childhood. In early adolescence, girls had higher odds of obesity and a higher fat mass index than boys. During late adolescence, a higher fat mass index was observed for girls compared with boys.
Higher risk scores associated with earlier pubarche, peak height velocity
Each 1 standard deviation increase in PCOS polygenic risk score was associated with a 0.85-month younger age at first pubarche for ALSPAC and Holbaek Study participants. Among those from the ALSPAC and Project Viva cohorts, a higher polygenic risk score was associated with a 0.64-month younger age at peak height velocity. No differences between boys and girls were observed with these associations.
When the study participants were split into quintiles by PCOS polygenic risk score, those in the highest quintile had a more rapid increase in BMI z score from age 7 to 10 years than those in the bottom quintile (beta = 0.026; 95% CI, 0.009-0.042; P = .003).
“The association between genetic risk for PCOS and the growth and developmental traits, age at pubarche and peak height velocity, persisted even after adjusted for BMI, suggesting the presence of BMI-independent biological pathways,” Zhu said.
Zhu said more research is needed to assess the mechanisms behind the associations found in the study.
“With ongoing collaborations, we hope to use computational genetic methods to implicate the biological pathways driven by specific PCOS genetic variants or groups of variants,” Zhu said.
For more information:
Jia Zhu, MD, can be reached at jia.zhu@childrens.harvard.edu.
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