MCPH1 & cranial volume in Chinese

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A common SNP of MCPH1 is associated with cranial volume variation in Chinese population:

Microcephaly (MCPH) genes are informative in understanding the genetics and evolution of human brain volume. MCPH1 and abnormal spindle-like MCPH associated (ASPM) are the two known MCPH causing genes that were suggested undergone recent positive selection in human populations. However, previous studies focusing only on the two tag single nucleotide polymorphisms(SNPs) of MCPH1 and ASPM failed to detect any correlation between gene polymorphisms and variations of brain volume and cognitive abilities. We conducted an association study on eight common SNPs of MCPH1 and ASPM in a Chinese population of 867 unrelated individuals. We demonstrate that a non-synonymous SNP (rs1057090, V761A in BRCA1 C-terminus (BRCT) domain) of MCPH1 other than the two known tag SNPs is significantly associated with cranial volume in Chinese males. The haplotype analysis confirmed the association of rs1057090 with cranial volume, and the homozygote males containing the derived alleles of rs1057090 have larger cranial volumes compared with those containing the ancestral alleles. No recent selection signal can be detected on this SNP, suggesting that the brain volume variation in human populations is likely neutral or under very weak selection in recent human history.

They used EHH & iHS. Also, they suggest that the derived form of rs1057090 is very ancient (the SNP has a very small window of linkage disequilibrium around it).

Related:
This is Bruce Lahn’s brain on ASPM and MCPH1, Did Modern Humans Get a Brain Gene from Neandertals?, Microcephalin & ASPM and Selection “controversy”.

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10 Comments

  1. Thanks for the update.

  2. Is the full text freely accessible anywhere? 
     
    No recent selection signal can be detected on this SNP, suggesting that the brain volume variation in human populations is likely neutral or under very weak selection in recent human history. 
     
    Wouldn’t balancing selection also look like this? I can’t see the full paper, so I’m curious whether they looked at heterozygotes and found either 
    – no effect on brain volume at all 
    – a smaller effect which didn’t reach statistical significance 
    Generally speaking the statement that brain volume variation is under only weak selection seems implausible to me. It’s certainly possible for an increase in brain volume to have no positive effect on fitness – I imagine that the positive correlation between brain volume and intelligence is contingent on some very specific, localized increases to volume and not on some general effect where more brains always make you smarter. However, the fitness *downside* to brain volume (increased dietary needs, perhaps increased difficulty of birth if the effect is seen even neonatally) is going to occur regardless of whether the extra gray matter is useful. Taking that into account and looking at the population frequencies for the SNPs in question I would lean more towards balancing selection as an explanation; I can’t believe that brain volume variation is fitness neutral.

  3. Thanks for the link, razib. The lack of effect in the females in the study is striking. I thought perhaps they just didn’t have a good enough p-value due to fewer women or something but no, it looks pretty clear that there simply isn’t an effect on that side. 
    The magnitude of the effect also surprised me – they calculate nearly 100cc greater brain volume on average (homozygous for derived vs homozygous for ancestral allele). That’s enough to matter metabolically – you’re talking about ~2% greater calorie consumption (ballpark figure) due to the increased brain size. Neutral fitness is not the same thing as no effect…

  4. bbartlog says: “The lack of effect in the females in the study is striking. I thought perhaps they just didn’t have a good enough p-value due to fewer women or something but no, it looks pretty clear that there simply isn’t an effect on that side.” 
     
    Schoenemann et al found no within-family association between brain size and IQ for sisters. Maybe this ties in to the larger male variance, the size-IQ connection is sex-mediated somehow…

  5. The confidence interval in Schoenemann et al. does not preclude a substantial within-family correlation.

  6. Hey, is Malloy on vacation? Haven’t seen him post in a while.

  7. Update the forum everyday. :)

  8. Stephen Jay Gould sure would have liked this data! 
     
    I would like to point out that the racial allelic frequencies for this SNP are the opposite of what is predicted by Rushton’s theory of racial genetic differences in brainsize, since Rushton claims that brainsize is largest in Chinese/Japanese, medium in Europeans, and smallest in Africans.  
     
    The allelic frequencies for the supposed brainsize-increaser allele (the derived C allele): 
     
    Perlegen AFD data- 
     
    0.239 Chinese 
     
    0.542 European 
     
    0.636 African American 
     
    HapMap data- 
     
    0.422 Chinese 
     
    0.284 Japanese 
     
    0.508 European 
     
    0.608 African

  9. What’re the effects of diet on cranial volume?

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