<i>PCSK1</i> polymorphisms association with obesity incidence during a 20-year follow-up of the CARDIA study.

<p>Controls: participants followed 20 years and remaining non-obese (BMI<30 kg/m²) over the 20 years.</p><p>Cases: incident cases of obesity over the 20 years.</p><p>HR: hazard ratio.</p><p><i>P</i>-values are adjusted for gender and center.</p

Genotype distributions of the two <i>PCSK1</i> variants in the MESA study.

<p><i>P</i>-values are adjusted for age, gender, center and the first 10 principal components.</p><p>NA: not available.</p

Contribution of Common <em>PCSK1</em> Genetic Variants to Obesity in 8,359 Subjects from Multi-Ethnic American Population

<div><p>Common <i>PCSK1</i> variants (notably rs6232 and rs6235) have been shown to be associated with obesity in European, Asian and Mexican populations. To determine whether common <i>PCSK1</i> variants contribute to obesity in American population, we conducted association analyses in 8,359 subjects using two multi-ethnic American studies: the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). By evaluating the contribution of rs6232 and rs6235 in each ethnic group, we found that in European-American subjects from CARDIA, only rs6232 was associated with BMI (<i>P</i> = 0.006) and obesity (<i>P</i> = 0.018) but also increased the obesity incidence during the 20 years of follow-up (HR = 1.53 [1.07–2.19], <i>P</i> = 0.019). Alternatively, in African-American subjects from CARDIA, rs6235 was associated with BMI (<i>P</i> = 0.028) and obesity (<i>P</i> = 0.018). Further, by combining the two case-control ethnic groups from the CARDIA study in a meta-analysis, association between rs6235 and obesity risk remained significant (OR = 1.23 [1.05–1.45], <i>P</i> = 9.5×10⁻³). However, neither rs6232 nor rs6235 was associated with BMI or obesity in the MESA study. Interestingly, rs6232 was associated with BMI (<i>P</i> = 4.2×10⁻³) and obesity (<i>P</i> = 3.4×10⁻³) in the younger European-American group combining samples from the both studies [less than median age (53 years)], but not among the older age group (<i>P</i> = 0.756 and <i>P</i> = 0.935 for BMI and obesity, respectively). By combining all the case-control ethnic groups from CARDIA and MESA in a meta-analysis, we found no significant association for the both variants and obesity risk. Finally, by exploring the full <i>PCSK1</i> locus, we observed that no variant remained significant after correction for multiple testing. These results indicate that common <i>PCSK1</i> variants (notably rs6232 and rs6235) contribute modestly to obesity in multi-ethnic American population. Further, these results suggest that the association of rs6232 with obesity may be age-dependent in European-Americans. However, multiple replication studies in multi-ethnic American population are needed to confirm our findings.</p> </div

Obesity incidence, by age at baseline in European-Americans from CARDIA according to the rs6232 genotype.

<p>The proportion with obesity was calculated within each genotypic class to assess the impact of the genotype on obesity incidence. An increase incidence of obesity was confirmed by Cox survival analysis (adjusted for gender and center) among TT and CT carriers during the 20 years of follow-up (hazard ratio 1.53 [1.07–2.19], <i>P</i> = 0.019).</p

Description of the populations used for association analyses.

<p>Description of the populations used for association analyses.</p