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One of the important questions plaguing most women during their middle age is whether they should opt for menopausal hormone therapy to alleviate menopausal symptoms.
Many women in this delicate phase count fretfully the number of sleepless nights, the night sweats and hot flashes that interrupt their otherwise normal life.
The U.S Centers for Disease Control and Prevention analyzed a 2015 National Health Interview survey (NHIS) and found that over 56% of perimenopausal women failed to get sufficient sleep.
The dwindling levels of estrogen has been associated with the classic symptoms of menopause, which led people to believe that menopausal hormone therapy could lower the intensity of symptoms.
This made estrogen supplementation very popular during the late 1960s with the belief that it could make women ‘young forever’.
FDA approval for estrogen therapy for osteoporosis helped gain confidence of more women, with observational studies conducted in 1990s showing reductions in coronary heart disease and Alzheimer’s.
The first study that raised an alarm about the use of menopausal hormone therapy and breast cancer risk was the Women’s Health Initiative study. This study found that for every 10,000 person-years of use of menopausal hormone therapy (MHT) use, there were 8 more invasive breast cancers.
Estrogen is a female hormone which is mostly produced in the ovaries. During breast development, the DNA present in the cells is constantly copied before the development of new breast cells.
This delicate process could increase the risk of development of genetic abnormalities.
Estrogen plays an important role in breast tissue development and supplementation with this hormone during menopause, therefore, has been shown to be associated with an increased risk for breast cancer.
The results of the Women’s Health initiative study led to a considerable drop in the use of hormone therapy in the U.S.
The assumption was that women would use it for a short period of time with the risk of breast cancer being uniform.
However, a large study conducted by the Breast Cancer Association Consortium on perimenopausal women showed that specific genetic variants modified the effect of hormone therapy use on the risk of breast cancer.
The study included a large sample size and three loci present on the chromosomes 13, 14 and 16 were found to alter breast cancer risk on menopausal hormone therapy use.
Women who had more than 5 or 6 high risk variants were found to have an 86% increased risk for breast cancer on MHT use while there was no association with breast cancer risk on MHT use among women with fewer than 2 risk variants.
The results of the study should stress the importance of identifying genetic variants and weighing the relief of symptoms against the unhealthy legacy of taking these medications.
You can now find out if you carry the variants associated with Menopausal hormone therapy and breast cancer risk from Xcode’s Breast Cancer report by uploading your 23andMe or any other Ancestry DNA raw data.
You can read more about the Xcode Breast Cancer report here.
When 23andMe receives your saliva sample, it extracts cells (mostly cheek cells) from your saliva, then breaks down the cell and nucleus to get your DNA. Your DNA is then purified and multiplied several folds to make it easily detectable.
23andMe uses a “genotyping chip” to detect your DNA data. What part of your DNA is detected depends on which chip was used. 23andme has used different chips over the years. Think of it in terms of smart phones. Each year, new versions of chips are released with more and more functionality than the previous version. Similarly, the DNA chips are constantly upgraded and the latest “chip” is typically better than the previous version in terms of how much information it detects from your DNA.
In 2017, 23andMe migrated from the Illumina OmniExpress chip that was used across multiple ancestry DNA companies. The current 23andme v5 chip, the Global Screening Array (GSA) is a next-generation genotyping array for population-scale genetics, variant screening, pharmacogenomics studies, and precision medicine research. This version of the chip has around 650,000 SNPs suitable for both ancestry and health testing.
Keep in mind that 23andme includes a list of their own unique features to the standard GSA chip.
According to Illumina, the GSA covers a multi-ethnic, genome wide markers with curated clinical research variants and markers that serve as quality control for precision medicine research. The content has been selected for high imputation accuracy specifically to the minor allele frequencies above 1%. All the 26 1000 Genomes Project populations have been considered. The balance between the health and ancestry markers is evident in that, variants with established associations with diseases, pharmacogenomic relevance have been included. The content is curated based on ClinVar, National Human Genome Research Institute (NHGRI), PharmGKB, Exome Aggregation Consortium (ExAc Database). In-built quality control markers enable sample identification for applications in large scale genomics and screening, which is very useful for companies with a huge customer demand like 23andMe.
The Illumina Omniexpress chip, is the current chip version for other popular companies like Ancestry DNA and Family Tree DNA. However given the demand for third party re-analysis from companies like Xcode Life, and GSA’s compatibility with these tools, all other ancestry companies are likely to migrate to this version. While the OmniExpress chip was satisfactory for the European populations, it could not be applied to the other populations. The GSA is more inclusive of other world populations.
Because there are so few overlapping markers between the GSA and the OmniExpress this change will also present problems for companies and third-party websites that accept autosomal DNA transfers. A choice will need to be made as to whether to do comparisons using only the overlapping markers or whether to experiment with imputation. Xcode’s platform caters to all major genotyping platforms across the ancestry DNA testing companies.
Those of you who purchased the 23andMe kit after August 2017, will have reports based on Illumina’s latest v5 chip. Given that this chip is the most conducive with health-related traits, let’s take a look at a list of all traits that you can do from the raw data file:
| CHIP | NAME | NO. OF SNPs | Applications |
| 23andMe | Major categories | ||
| v1 | HumanHap550+ | 576,000 |
|
| v2 | HumanHap550+ | 597,000 | |
| v3 | HumanOmniExpress+ | 992,000 | |
| v4 | HTS iSelect HD | 611,000 | |
| v5* | Global Screening Array (GSA) | ~650,000 | |
| Ancestry DNA | |||
| v1 | OmniExpress Genotyping BeadChip | 701,400 | |
| v2* | OmniExpress Plus Genotyping BeadChip | 669,000 | |
| Family Tree DNA | |||
| - | OmniExpress microarray chip | 696,800** | |
| Living DNA | |||
| - | Global Screening Array (GSA) | ~650,000 | |
| MyHeritage | |||
| - | OmniExpress microarray chip | 696,800** | |
*current chip
**Only for autosomal and the X chromosome
A haplogroup is a global extension of your family. Depending on the sequence of genetic markers that they carry in their cells people can be grouped into specific ancestry DNA haplogroups. A group of individuals belonging to the same haplogroup can trace their roots back to a common ancestor. This usually also points to a specific geographical point since each haplogroup has a definite migratory pattern. If you want to know more about the science behind these ancestry DNA haplogroups, you can refer here
Besides their common geography and migratory pattern haplogroups are characterized by a de novo mutation. These mutations are carried and undergo vertical transmission through subsequent generations. When sufficient number of people carry this single base change in their DNA sequence they will together form a haplogroup. Needless to say that it takes thousands for sufficient individuals to carry the mutation (now called polymorphism) and form a haplogroup.
Haplogroups are not permanent. They have in the past phased-out and formed new ones. Though some of them have successfully sustained themselves to the present day. Nearly 50% of all Europeans have the haplogroup H. This means that they have all descended from a single person who had lived thousands of years back.
The head of the maternal or paternal haplogroup within whom the set of gene variation first occurred.
New haplogroups are formed when a gene mutation occurs in someone from a particular ancestral clan. However, it is not before many generations that enough people carry the mutation for it to spread, become prevalent to be considered as a haplogroup. Any haplogroups that start forming today will not be recognized as new ones for centuries, or even millennia. The haplogroups that form today will eventually be able to be traced back to the earliest known person to carry the mutation, just as today’s known haplogroups can be traced back to the earliest known person to carry it in the distant past.
Everyone inherits the DNA within a cell organelle called the mitochondria from the mother only. Hence maternal haplogroups are defined using variants in an individual’s mitochondrial DNA. Another interesting fact about the mitochondrial DNA is that it does not undergo the process of recombination with other types of DNA (like your nuclear DNA). This means it is inherited as it is with limited changes directly from you mother. Therefore individuals with the same maternal line will share the same maternal haplogroup. Each maternal haplogroup traces back to a single mutation at a specific location and time.
Y chromosome is found exclusively in males (with the exception of individuals with Klinefelter’s syndrome). The Y chromosome undergoes genetic recombination with the X chromosome at a specific region called the pseudoautosomal region. In other words, this region of the Y chromosome behaves like an autosome in spite of being a sex chromosome. However this a very small fraction. Around 95% of the Y chromosome remains unchanged across generations. This is used to trace your paternal ancestry. Though females do not have a Y chromosome, they would share the same paternal haplogroup with another male member of the direct line (e.g father, brother).
