Aims: To replicate findings in the 1982 Pelotas cohort relating to the association of ADIPOQ SNPs and metabolic traits

Hypothesis: Adiponectin (ADIPOQ) polymorphisms are associated metabolic traits in both Pelotas 1982 cohort and ALSPAC.

Variables:

rs6810075 (ADIPOGEN hit)

rs2241766 (may require imputation)

rs266729

rs1501299

HDL-cholesterol

LCL-cholesterol

Total cholesterol

C-reactive protein

Waist circumference

Glucose

Insulin

Triglycerides

Mean Arterial Blood Pressure

BMI

Adiponectin

The question: Are candidate SNPs in the ADIPOQ gene associated with metbolic traits in the ALSPAC cohort and do associations replicate those observed in the Pelotas 1982 cohort?

The rationale: Early SNP studies in the Pelotas 1982 cohort indicate an association between ADIPOQ SNPs (rs2241766, rs1501299, rs266729) and measures of metabolic health, in particular waist circumference and triglyceride levels. These findings are in accord with the recent multi-ethinc meta-analysis of adiponectin levels and their influence on T2D and metabolic traits [PLoS Genet 2012; 8(3): e1002607], to which ALSPAC contributed, although different SNPs have been analysed in the Pelotas cohort. ALSPAC has the data available to readily undertake a replication of the associations observed in Pelotas thereby adding both power and biological weight to the hypothesis.

SNPs analysed in 1982 Pelotas cohort and relationship to main ADIPOQ SNP reported in recent meta-analysis;

rs6810075 x rs266729, D' 0.956, r2 0.676

rs6810075 x rs1501299, D'0.896, r2 0.172

rs6810075 x rs2241766 (not in HapMap)

rs266729 x rs1501299, D' 0.875, r2 0.121

Analysis plan:

1. Obtain above listed data from ALSPAC, including imputation of SNP (rs2241766) if required

2. Assess associations between listed SNPs and metabolic outcome variable listed, recapiltulating analysis plan already conducted on Pelotas 1982 cohort data

3. Meta-analyse where variables allow

As a parallel activity data will be requested from ADIPOGEN relating to the association of the 1982 Pelotas SNPs to adiponectin levels in the consortium data (both with and without ALSPAC data included)

Nic Timpson has offered to assit with analysis of ALSPAC data.