Discussion
PROLIFERATION, GIANT, MINOR
These data show that males in the LACE cohort with at least one minor allele for either rs10783486 or rs2854464 were taller than those homozygous for the major allele and had more arm fat but we did not see any associations of these alleles with body composition in females. Previous studies have shown that polymorphisms in Previous studies have shown that muscle strength measured as grip strength or leg strength are proportional to height [The associations that we identify with height were not identified in the previous studies of these alleles and are not apparent in the GIANT consortium at p<10Although our data cannot demonstrate causality, they raise the possibility that the accumulation of extramuscular limb fat may be influenced by activin receptor signalling—a hypothesis consistent with known effects of both myostatin and activin. Previous studies have shown that activin A signalling increases the proliferation of adipocyte progenitors but reduces adipocyte differentiation [Small numbers in our analysis limit our ability to draw strong conclusions about differences between males and females, but it is possible that the difference in fat accumulation may be either more detectable in males due to differences in relative fat proportions, or may be larger in males than in females. It is possible that the increase in fat is a consequence of reduced relative strength and activity, or is due to a difference in muscle metabolism that contributes to the difference in strength but leads to a greater resistance to insulin over time and therefore an increase in the accumulation of fat that accompanies this. However, even though the median strength of the rs10783486 GG individuals was higher than that of the AA/AG individuals, consistent with the known associations of this polymorphism [The greater height in those carrying the minor allele is more difficult to rationalise if the minor alleles are associated with higher ACVR1B protein levels as both activin and myostatin inhibit bone growth [