Are you there God? It's me, and I have another question.

ResearchBlogging.orgIf you are an American woman of a certain age, chances are that like me your first written introduction to reproductive biology was with Judy Blume.  I was thinking back to that time this weekend as I came across several papers in Nature Genetics that addressed the timing of certain female-affecting SNPs.  Unfortunately I found that I would have preferred Judy Blume to the guidance I got from these papers.  A copy of her book would have been dramatically more cost effective for me.

The first two papers address variants that are associated with age at menarche.  The authors of both papers begin by describing age at menarche, which is approximately 13 years in the US for girls of Euro ancestry, and slightly earlier for African-American girls (Sulem et al give a bit more detail).  They talk about the risks of early or late menarche.  Both papers touch on issues of BMI or body mass and or height as related issues.  The Sulem paper describes the drop in average age from 16 years in the nineteenth century–likely from environmental factors.  It’s all very informative in a general sense.  But how are they getting the reports of first periods from study participants–”adult recalled”?  I mean, I know some people kept diaries and maybe some people wrote it down, but really–even in a place with national medical records these numbers have to be fuzzy at best.  And if there is such a large environmental component tied to nutrition or obesity, how can you conclude from that?

Anyway, the work goes on to describe fairly standard techniques for identifying loci of interest.  The Perry et al paper finds 2 separate regions of interest: 9q31.2 and 6q21.  Sulem et al find the 6q21 region.  The 9q signal was associated with a 5 week reduction in menarcheal age.  5 weeks?  From largely adult recalled data?  Ok.  I guess.  The same group also finds a 5 week window for the 6q signal.  Huh.  5 weeks again.   The Sulem team find the 6q signals have effects that are 1.2 months (ah, 5 weeks?) or .9-1.9 months for a second allele in that region.  Both groups list adjacent genes that could be affected–but certainly there were no smoking guns.

If you are looking for anything helpful for working with girls in your life, get Are You There God? It’s Me, Margaret.  Because there’s really nothing actionable in these papers.

The other paper that caught my eye was by Stolk et al (Stolk was also an author on the Perry paper): Loci at chromosomes 13, 19, and 20 influence age at menopause.  They begin by illuminating me on the various risks associated with this (cancer, heart disease, osteoporosis).  We have an even bigger age range for this process–age 40-60, with an average of 51 years. Again we have a self-reporting age from participants.  We get a signal in these several regions, and again a list of adjacent genes without anything definitive. The outcome is about a 19% increased risk for menopause before age 50–for each of the regions.  How…similar. After re-examining the data to account for some environmental factors (like BMI, contraceptive and horomone use) the data was unaffected.

I actually appreciate this work–I’m glad someone is looking at women’s health issues.  I firmly believe that the next really interesting data is going to come from temporal and spatial gene expression that the pure genomic data won’t reveal.  But I guess I wanted more–something actionable, something I could do with this.  But I know how this works and I’ll deal with the not knowing.  I wonder how people will take this sort of information when they have their genomes done.  Will they scan their sequences for these SNPs?  Will they worry about that 19% chance for themselves, or that 5 weeks for their daughters?  What will they do with that information?   It will be interesting to see.

Personally I was just wishing Judy Blume wrote a menopause book.  But I don’t see one….Are you there God?  I have a subsequent and related question….

Perry, J., Stolk, L., Franceschini, N., Lunetta, K., Zhai, G., McArdle, P., Smith, A., Aspelund, T., Bandinelli, S., Boerwinkle, E., Cherkas, L., Eiriksdottir, G., Estrada, K., Ferrucci, L., Folsom, A., Garcia, M., Gudnason, V., Hofman, A., Karasik, D., Kiel, D., Launer, L., van Meurs, J., Nalls, M., Rivadeneira, F., Shuldiner, A., Singleton, A., Soranzo, N., Tanaka, T., Visser, J., Weedon, M., Wilson, S., Zhuang, V., Streeten, E., Harris, T., Murray, A., Spector, T., Demerath, E., Uitterlinden, A., & Murabito, J. (2009). Meta-analysis of genome-wide association data identifies two loci influencing age at menarche Nature Genetics DOI: 10.1038/ng.386

Stolk, L., Zhai, G., van Meurs, J., Verbiest, M., Visser, J., Estrada, K., Rivadeneira, F., Williams, F., Cherkas, L., Deloukas, P., Soranzo, N., de Keyzer, J., Pop, V., Lips, P., Lebrun, C., van der Schouw, Y., Grobbee, D., Witteman, J., Hofman, A., Pols, H., Laven, J., Spector, T., & Uitterlinden, A. (2009). Loci at chromosomes 13, 19 and 20 influence age at natural menopause Nature Genetics DOI: 10.1038/ng.387

Sulem, P., Gudbjartsson, D., Rafnar, T., Holm, H., Olafsdottir, E., Olafsdottir, G., Jonsson, T., Alexandersen, P., Feenstra, B., Boyd, H., Aben, K., Verbeek, A., Roeleveld, N., Jonasdottir, A., Styrkarsdottir, U., Steinthorsdottir, V., Karason, A., Stacey, S., Gudmundsson, J., Jakobsdottir, M., Thorleifsson, G., Hardarson, G., Gulcher, J., Kong, A., Kiemeney, L., Melbye, M., Christiansen, C., Tryggvadottir, L., Thorsteinsdottir, U., & Stefansson, K. (2009). Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche Nature Genetics DOI: 10.1038/ng.383