SNPWatch: Do These Genes Make My Brain Look Big?

If you have a big head, you may be subjected to a fair bit of teasing, but science may offer you some consolation. For instance, individuals with a smaller intracranial volume (the area within the skull) are at slightly higher risk for late-life dementia. In addition, a smaller hippocampus (a section of the brain involved in learning and memory storage) has been associated with Alzheimer’s disease and mental illnesses such as depression and schizophrenia. Four papers published recently in Nature Genetics address various measures of head size and their possible health implications.


Factors influencing infant head circumference
An international team of scientists, led by H. Rob Taal from the Erasmus Medical Center in the Netherlands, has attempted to answer the question that has plagued numerous women in labor — why is my baby’s head so large?

Head size as an infant is highly heritable, meaning genetics accounts for a large portion of infant head circumference variability. To determine which genetic factors are involved, the team of researchers looked at genetic data from over 19,000 infants with European ancestry. They found that, on average, infants with the CC genotype at in the HMGA2 gene had heads that were approximately 1 mm larger around than infants with the CT genotype, and infants with the TT genotype had on average heads that were 1 mm smaller around. In addition, they found that each A at in SBNO1 gene was associated with approximately 1.2 mm larger head circumference.

Both of these SNPs are associated with height in adults. SBNO1, however, may play more of a role in neurological development; a similar gene found in fruit flies is related to development of a fly’s central nervous system.

Factors influencing intracranial volume
Early in life, brain volume and skull size are highly correlated. However, at a certain point the brain stops growing and begins to shrink while the skull remains the same size. Intracranial volume, which is the volume within the skull, is thus considered a good proxy for an individual’s maximum adult brain size.

Two of the recent Nature Genetics papers studied genetic factors influencing intracranial volume. A group of researchers led by Jason Stein from David Green School of Medicine at the University of California, Los Angeles, discovered that the SNP within the HMGA2 gene on chromosome 12 is associated with intracranial volume. The study, which used magnetic resonance imaging (MRI) to measure the skull size of over 15,000 individuals of European ancestry, suggests that the CC genotype at is associated with a 9.1 mL increase in intracranial volume over individuals with the CT genotype, and that the TT genotype was associated with a 9.1 mL decrease in intracranial volume.

Although the HMGA2 gene has been associated with height, this did not seem to fully account for the observed association between the SNP and intracranial volume. In a smaller, follow-up analysis the researchers also found that the C version of this SNP was associated with a very slight increase in IQ. But don’t “get a big head” about it if you happen to be CC at this SNP — the evidence was fairly weak and more research is needed to confirm these findings.

Another large team of researchers, led by M. Arfan Ikram, from the Erasmus Medical Center in the Netherlands, found two other SNPs influencing intracranial volume: on chromosome 6 and on chromosome 17. Each G at was associated with a 12.5 mL increase in intracranial volume, and each G at was associated with a 15 mL decrease in intracranial volume in a study of nearly 82,000 elderly individuals of European ancestry.

Factors influencing hippocampal volume
The hippocampus is a segment of the brain involved in learning and storing memories, and the size of the hippocampus has medical significance. A smaller hippocampal volume has been associated with depression, schizophrenia, and types of epilepsy. In addition, the hippocampus is often one of the first areas of the brain to be affected by Alzheimer’s disease, making it an early indicator of this disease.

A team of researchers led by Joshua C. Bis from the Department of Medicine at the University of Washington in Seattle looked at over 19,000 people with European ancestry and found that the C version at near the HRK-FBXW8 gene is associated with a 0.11 mL increase in hippocampal volume. Since the hippocampus shrinks as one ages, the authors equated this hippocampus size difference to a decrease of 3.9 years of age.

Curious about your brain genetics but not yet a customer? Join 23andMe today to learn more about your ancestry and health!

If your head is larger than most, be grateful for your possible lower risk of certain diseases and potentially higher IQ. But don’t let it go to your head — perhaps you should thank your parents for your big-head genes. Indeed, given the trouble your big noggin caused her, perhaps you should especially thank your mother this Mother’s Day!

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.






  • Diane Van Hoose

    Why are there no 23andme survey questions regarding autism spectrum, and specifically Asperger’s syndrome to further research in this area that affects 1 in 88?
    Thanks,
    Diane

    • http://23andme.com Shwu

      Hi Diane,

      Thanks for your suggestion — we’ve passed it on to our research team. You can always suggest research topics directly by emailing we@23andme.com or through the “Suggest your question topic” link at the top of this page: https://www.23andme.com/you/23andwe/questions/.

      Thanks for reading The Spittoon!

  • Brownie High (MacKie)

    Interestingly enough, I DO have a larger head than most women. I wear a size larger in a hat than the average woman. My dad also had a big head. To compensate, we had small hands and feet. :-)

  • Cindy Beam

    Well, this is certainly interesting. I have never felt that my head was any larger than normal, but both of my children had larger than average heads, at birth. (Woe is me!) However, I do have epilepsy.

  • John Lerch

    OTOH the singer from the 50′s Theresa Brewer was reported to have a head circumference larger than her waist–24 inches. And she died fairly young 72 of some degenerative brain disease I had never heard of.

  • Amy Stephenson

    I found the information interesting but in my case slightly inaccurate. I actually have a small head, literally as an adult I can comfortable wear a hat that would fit the average 8 year old girl! However, I am considered of more than average intelligence. Maybe a study needs to be done on this combination.

  • Michael Tate

    My genes, according to the research, say I should have a smaller skull & intercranial size. I was a C-section baby and have a somewhat larger than normal size skull. Eye wear requires me to have size 11 temples and I’ve yet to find a large enough hat.

  • Stephen Baird

    My hat size is 7 3/4, so my head is bigger than average but my genes don’t show it.

  • Heather D

    My genetic profile shows that I should have an average to larger head – but my head is tiny! I am a 5’6″ adult woman, yet I wear a child’s bike helmet because the women’s helmets were too big. My grandmother had a smaller head and had Alzheimer’s.

  • James Beall

    ~

    Hi,
    My head is definitely over sized. Hat size = 8 3/8″, and yes, I was teased a little about it as a kid.
    My I.Q. is “Un-testable” officially, but has been estimated to be >300-340.

    But your gene readouts on me on this page do not indicate it being that far removed from the norm.

    I think that you have some more genes to find.

  • Flupke

    @ Diane

    I definitly support your suggestion
    It has already been discussed many times on 23andme.com
    Dunno why it never came out

  • Justin Loe

    Although the snp results suggest normal head size, my head size is significantly above average. It could be evidence of geological formations inside. Probably just some rocks.

  • marty

    my brother had a spect scan done at dr. amen’s office in WA state. it showed that his hippocampus was very small, he couldn’t take care of himself and was diagnosed yrs ago with schizophrenia. although they didn’t tell us he had it, it was suggested that he might have it.
    he has always had a high i.q. but being given up for adoption at age 3 does things to a childs mind. also having a manic depressive adoptive mother changed who he ended up being.
    i’d like to see the reseachers research people who have ptsd.
    which is something one cannot add when doing these surveys.

  • Arlene

    I don’t know how to interpret the info: First snp says head smaller, 2nd snp says larger, and so it goes, smaller, larger depending on the chromosome? Then larger hippo volume at end, but then smaller followed by larger intracranial volume. Admit I’m no scientist but is this a wash? If snps not consistant then what?

  • John Fernandez

    I do have a large head. Ihave a US size 8 hat size. I also have large feet with a US size 15. SNPrs4273712 states that I have 12ML larget cranial volume but the other SNP’s say I have average volume. I am not sure how to differentiate which is which.

  • Daisy

    I have a larger head than normal, hat size 7 1/2 but for me I see all “typical-size” genes. Maybe I should have been taller…was my growth stunted? If so, too bad. I would have liked to be taller.

    Hey, Brownie High — I, too, have small feet and hands. We may have the large-head-small-feet-and-hands syndrome.

    My husband, who has a small head, is also almost completely typical in the gene department, except for 15 ml smaller on rs2532274. Of my three kids, two are large-headed and one is small-headed.

  • Judi

    Can I ask how head circumference or hat size correlates to cranial volume?

  • http://angelagweber@aol.com angela

    I have an enormous head, am tall, small framed, have unnoticeable skeletal abnormalities (pectus excavatus, corrected extreme pronation, and mild scoliosis) and have small hands and feet. However, the bulk of the skull circumference is the occipital bun. I believe that there is some proclivity for scandanavians to have a large occipital bun which is bone and does not reflect an increased size of cranium.
    Does anyone know about that?

  • Margaret

    I have a large head, appx size 8 hat and also have a high IQ with test scores between 130-150. I always thought I was a stranger in my family…odd person in the group. Just FYI.

  • Fabian

    My genes TT = smaller intracranial volume.

    The fact: Far more than average. European size: 62 cm. The larged helmet of 150 recruits. My doctor: Big brain on your X-ray..
    Mother: big brain. Father: quite small brain.

  • carlos

    After long hours of meditation i only have reached a conclussion: If you have a big head, you need a big hat, logically more expensive than a small one, that’s all. Be careful with these ways of thinking. Dr Watson, one of the discoverers of DNA, I believe to remember said unfortunate afirmations about intelligence and races, and there has been also Nobel prices for black people.
    A French politician of XIX century, I think Leon Gambetta, I believe to have read he had a small head and but was a fabulous speaker.

  • Tonya

    Well this study is flawed since it only used European babies…doesn’t apply to anyone else but Europeans (i.e. not most of the world).

  • Chris

    My head is large enough to qualify as macrocephaly on wikipedia (> 60cm) yet the genes listed above seem to be a wash as to the fact my head is much larger than average.

  • Juan Carlos Zuazo

    I’ve definitely got a big head. I remember having checked my mother’s and her father’s skull X-rays, as well as mine. All three of them were incredibly similar in size and shape. All I can say about the three, in common, is that we were very sensiive and emotional, enjoying poetry and things like that; no IQ beyond imagination especially when we analise accomplishments in life.

  • David

    As a child I was always teased as having a big head. Even recently, while attending a funeral, childhood friends mentioned: You still have a big head, I could recognize you anywhere: 50 years later!

  • Finndian

    I was called Mel as a kid… short for mellon. My head is now about 8 1/4 but I’m 6’3″ 220lbs so it fits now. I read that some of the most famous people in history had enormous heads when I was a teenager and suddenly it was all right with me. I pulled out that fact ever time I heard comments about my head and forehead. My IQ is about 130.

  • Jennifer

    I have a Chiari malformation with syringomyelia. I’m looking forward to seeing if there will be any studies about having a bigger cerebellum than the size of the skull back there can hold.

  • Lillianne

    It appears my hippocampus is HUGE. ROFL! And 12ml of intercranial volume. Others are typical and average. Okay. :)

    Um, James Beall? Your I.Q. is estimated to be GREATER than 300? I’m sorry. I’m guffawing so heartily I can’t type. XD

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