Genetic architecture of plasma adiponectin overlaps with the genetics of metabolic syndrome-related traits.
OBJECTIVE
Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome-related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs).


METHODS
We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model.


RESULTS
Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin.


CONCLUSIONS
The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR.
Henneman
Peter
P
Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. c.vanduijn@erasmusmc.nl
Aulchenko
Yurii S
YS
Frants
Rune R
RR
Zorkoltseva
Irina V
IV
Zillikens
M Carola
MC
Frolich
Marijke
M
Oostra
Ben A
BA
van Dijk
Ko Willems
KW
van Duijn
Cornelia M
CM
D052242:Adiponectin / Q000097:blood* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics; D008076:Cholesterol, HDL / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D055815:Young Adult
D052242:Adiponectin; D008076:Cholesterol, HDL; D002097:C-Reactive Protein