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Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children
Licínio Manco1,2, David Albuquerque1, Beatriz Aranda1
1Research Centre for Anthropology and Health (CIAS), University of Coimbra, Coimbra, Portugal.
Insights
The proprotein convertase subtilisin/Kexin type 1 (PCSK1) gene variant rs6235 is linked to increased overweight and obesity risk in Portuguese boys. This finding suggests a sex-specific relationship between PCSK1 and childhood obesity.
Area of Science:
- Genetics and Molecular Biology
- Pediatrics
- Endocrinology
Background:
- The proprotein convertase subtilisin/Kexin type 1 (PCSK1) gene plays a role in appetite regulation.
- Previous studies on PCSK1 gene variants and obesity have yielded conflicting results.
- Investigating PCSK1 polymorphisms is crucial for understanding genetic contributions to obesity.
Purpose of the Study:
- To examine the association between four PCSK1 gene variants and the risk of overweight/obesity in Portuguese children.
- To explore potential sex-specific effects of PCSK1 variants on obesity-related variables.
- To analyze the relationship between PCSK1 polymorphisms and BMI Z-scores in a pediatric cohort.
Main Methods:
- A case-control study involving 685 Portuguese children aged 5-13 years.
- Analysis of four PCSK1 variants: rs6230, rs6232, rs6235, and rs3811942.
- Objective anthropometric measurements and BMI Z-score calculations using WHO standards.
Main Results:
- No significant association was found between the four PCSK1 variants and overweight/obesity risk in the overall population.
- A marginally significant association between the PCSK1 rs6235 variant (C-allele) and increased overweight/obesity risk was observed in boys.
- A significant interaction between the PCSK1 rs6235 polymorphism and sex for BMI Z-score was detected, with boys showing a sex-differentiated effect.
Conclusions:
- The study suggests a sex-differentiated association between the PCSK1 rs6235 polymorphism and overweight/obesity in Portuguese children.
- The rs6235 variant may influence obesity risk differently in boys compared to girls.
- Further research is warranted to elucidate the specific mechanisms underlying this sex-specific genetic effect on childhood obesity.
Objectives:
The proprotein convertase subtilisin/Kexin type 1 gene (PCSK1) is implicated in hypothalamic appetite control. Several studies have addressed the relationship between PCSK1 polymorphisms and obesity, although conflicting results were observed. We tested the potential association of four PCSK1 variants with the risk of overweight/obesity and related variables in Portuguese children.
Methods:
This is a case-control study, where four PCSK1 variants, rs6230 (c.-101T>C), rs6232 (p.N221D), rs6235 (p.S690T), and rs3811942 (c.*265T>C), were analyzed in Portuguese children (aged 5-13 years-old). Anthropometric measures were objectively collected and used to provide weight-for-age, height-for-age, and body mass index (BMI) for age. The indices generated were compared to standard reference values of WHO to obtain the corresponding Z-scores.
Results:
Logistic regression, in the dominant model, revealed no significant associations between the four individual PCSK1 variants and the risk of overweight/obesity in the total population. However, stratifying the sample by sex, a marginally significant association was found between the rs6235 minor C-allele and increased overweight/obesity in boys (n = 345) (OR 1.55 [1.01-2.38] p = .044), but not in girls (n = 340) (OR 0.73 [0.46-1.14] p = .169). Consistently, boys with genotype GG presented lower BMI Z-score (0.62) when compared to those with the genotypes GC + CC (1.04). Testing for different effects in males versus females, a significant interaction was found between the rs6235 polymorphism and sex for BMI Z-score (p = .025).
Conclusions:
Results of this study suggest for a sex-differentiated association between PCSK1 rs6235 and overweight/ obesity in Portuguese children.
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