Hunting a myostatin SNP-phenotype association

2 minute read

I happened to be reading some literature on myostatin today and ran across a recent paper (Kostek et al.2009).

Conclusion: MSTN 2379 A > G and FST -5003 A > T were associated with baseline muscle strength and size among African Americans only. These ethnic-specific associations are hypothesis generating and should be confirmed in a larger sample of African Americans.</div>

From that description, it looks like a gene-population association in the same vein as APOE, where an Alzheimer’s risk allele predicts disease incidence well in Europeans but not Africans. Myostatin regulates muscle growth, so here the idea would be that an allele has an effect that depends on genetic background, to the extent that might effect its evolution in those populations (Saunders et al. (2006) found that myostatin has two common alleles within Africa that look like they may have been recently selected, the two alleles are rare outside Africa).

Well, looking more deeply into the sample, we find that it’s not so impressive as it might look:

Results: Baseline MVC was greater among African Americans who were carriers of the MSTN G2379 allele (AG/GG, n = 15) than the A2379A homozygotes (n = 8; 64.2 6.8 vs 49.8 8.7 kg). African Americans who were carriers of the FST T-5003 allele (n = 12) had greater baseline 1RM (11.9 0.7 vs 8.8 0.5 kg) and CSA (24.4 1.3 vs 19.1 1.2 cm2) than African Americans with the A-5003A genotype (n = 14; P < 0.05). No MSTN or FST genotype and muscle phenotype associations were found among the other ethnic groups (P 0.05).</div>

Those tiny sample sizes (n = 15, n = 8) come from stratifying a much larger sample (n = 645) into ancestry groups. The very large European component of that large sample (n = 509) showed no gene-phenotype associations. What’s left is a significant result (p < 0.05) considering only 23 people.

This may not be unusual – this allele is rare in Europeans, so the two samples may be pretty close to each other in statistical power. But it’s not exactly a vote of confidence in favor of a large effect size for the allele, even within the small African-American sample.

That’s a common story in gene-phenotype association studies. Possibly it will replicate in a larger sample – and hopefully if it doesn’t replicate, somebody will still publish the result so that we’ll know about it.


   Kostek MA, et al. 2009. Myostatin and follistatin polymorphisms interact with muscle phenotypes and ethnicity. Medicine and Science in Sports and Exercise 41:1063–1071. doi:10.1249/MSS.0b013e3181930337.

   Saunders MA, et al. 2006. Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth. Am J Hum Genet 79:1089–1097. doi:10.1086/509707.