SNPwatch: Researchers Link Common Genetic Variations To Those Changes A Woman’s Body Goes Through

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

No matter when it happens, puberty is no fun.  But for girls, entering womanhood earlier or later than average can mean more than just the social awkwardness of being quick to mature or a late bloomer.  It can have important health consequences later in life.

In general, girls in the developed world are maturing faster now than ever before.  In the mid-nineteenth century the age at menarche (the first menstrual period, a milestone usually reached about two to three years after puberty begins) was about 16, but by the end of the twentieth century that number had fallen to about 13. Earlier age at menarche has been associated with an increased risk for breast, ovarian and endometrial cancer. On the other hand, later menarche is linked to increased risk for osteoporosis and cardiovascular disease.

Much of the change in the rate of maturation for girls has been attributed to better nutrition and rising rates of obesity, but new research shows that the age at menarche is also influenced by genetics.

Four papers (Ong et al., Sulem et al., Perry et al., and He et al.), published online yesterday in the journal Nature Genetics, analyzed data from a total of more than 60,000 women with European ancestry and identified two regions of the genome that contain variations associated with small differences in age at menarche.  One of these four studies, and a fifth paper (Stolk et al.), also found variations associated with the timing of menopause, the other end of the reproductive spectrum for women.

All four studies looking at age of menarche found a connection with a region of chromosome 6. Each paper identified slightly different variants, but they all appear to be zeroing in on a single, yet to be found, causative variation in the DNA.  As an example of the effect of the chromosome 6 SNPs, Ong et al. found that compared to those with two Cs, each T at rs314263 meant that woman got her first period about six weeks earlier.

(Ong et al. actually looked at rs314276, but we’re focusing on rs314263, a perfect proxy for the original SNP.  23andMe customers can check their data for rs314263 using the Browse Raw Data feature.)

Each T at rs314263 was also associated with 1.20 times greater odds of breast development at age 10, 1.26 times greater odds of advanced breast development between the ages of 9 and 16 and a faster rate of increase in height and weight.

Although girls who go through puberty earlier than their peers are tall for their age during childhood, their growth stops sooner and they are generally shorter as adults.  Ong et al. found that each T at rs314263 was associated with a reduction in adult height of about 0.15 inches.

Two studies also found an association between variations on chromosome 9 with age at menarche.  Each C at rs7861820 (the most significant SNP found in He et al.), for example, translated into about five weeks earlier menarche.

He et al. and Stolk et al. found variations in five regions of the genome associated with another big change in a woman’s life: menopause. The risks associated with the timing of menopause are the reverse of those associated with menarche: later menopause has been associated with higher risk for certain cancers and earlier menopause is linked to increased risk for osteoporosis and cardiovascular disease.

(23andMe customers can check their data for SNPs representative of these five regions using the table at the end of this post.)

Finally, all of you boys and men out there need not feel left out:  Ong et al. also looked at the effects of rs314263 on puberty in males.  They found that each copy of an T translated into 1.26 greater odds of advanced voice breaking at age 15, 1.19 times greater odds of advanced pubic hair at age 13, faster rate of growth at age 10 and about a tenth of an inch less in adult height.

SNPs Associated With Menopause

SNP Version Effect On Age At Menopause (compared to two copies of the other version)
rs16991615 A About 3.5 weeks later
rs1172822 T About 25 weeks earlier
rs365132 T About 20 weeks later
rs2153157 A About 15 weeks later
rs7333181 A About 27 weeks later

  • Phantom

    You say that “Ong et al. actually looked at rs314276, but we’re focusing on rs314263, a perfect proxy for the original”.

    Could you explain that a little more? How is one SNP a proxy for another? How can we know if it’s a perfect vs. partial proxy?

  • http://www.23andme.com ErinC

    The two SNPs, rs314276 and rs314263, are located very close together in the genome. In fact, they are close enough that according to our European reference set they always travel together from parent to child. The version of rs314276 that is associated with earlier menarche and the T version of rs314263 seem to always get passed down together as a pair, so we feel confident in telling you that rs314263 can be used as a substitute for rs314276. As you read more SNPwatch posts here in the Spittoon, you’ll see that we often use proxy SNPs when the variation reported in a paper is not currently available on the 23andMe SNP chip.

  • Allie from Albany

    Fix it so girls start later. I’d rather have cardiovascular disease or osteoporosis than any kind of cancer!!!!

    I started at 10 and a half, reached menopause at age 57, and was diagnosed with stage 3c ovarian cancer at age 58. If I’m lucky, I’ll live to 62.

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