This week, 23andMe updated its Carrier Status report on sickle cell anemia, an inherited red blood cell disease caused by the HbS variant in the HBB gene.
With this update, 23andMe’s Sickle Cell Anemia Carrier Status report* can now tell customers if they have two copies of the HbS variant, including what that may mean for their own health and the health of their children. Specifically, the report will inform these customers that they are at risk of developing symptoms of sickle cell anemia, and that they will pass one copy of the HbS variant on to each of their children.
“We are excited to release this updated report, which allows us to provide meaningful genetic information to a number of our customers,” said 23andMe Product Scientist Ruth Tennen. “More broadly, we hope our report can help raise awareness about sickle cell anemia, identify carriers who may otherwise not have known their status, and provide important educational information about sickle cell anemia and its health impacts.”
As part of this report update, 23andMe consulted with experts from Johns Hopkins University School of Medicine, Breaking the SSickle Cell Cycle Foundation, Morehouse School of Medicine, and the Sickle Cell Foundation of Georgia. These experts noted that the update of 23andMe’s Carrier Status report could help increase awareness about sickle cell trait and sickle cell anemia.
“23andMe is making genetic testing more accessible to anyone wanting to find out more information about their carrier status,” said Dr. Jason Payne, pediatric hematologist and sickle cell doctor at Morehouse School of Medicine.
What is sickle cell anemia?
Sickle cell anemia is a genetic condition caused by a specific genetic variant called HbS in a gene called HBB. The HBB gene contains instructions for making part of the hemoglobin protein, which is found in red blood cells and transports oxygen through the body. Inheritance of two copies of the HbS variant can lead to changes in the structure of hemoglobin, in certain situations. This can cause the hemoglobin to stick together and form long, rigid molecules that distort red blood cells into a sickle (crescent) shape. These sickled cells get destroyed prematurely, leading to anemia and symptoms such as fatigue. These cells can also get stuck in small blood vessels, which can lead to pain crises, frequent infections, and complications including kidney damage, acute chest syndrome, and stroke.1
Who is impacted by sickle cell anemia?
Sickle cell anemia affects people around the world. It is most common in people of African descent, but it also impacts people of Middle Eastern and South Asian descent, and people from the Caribbean, the Mediterranean, and parts of Central and South America. The HbS variant that causes sickle cell anemia is most common among people with ancestry from places where malaria is endemic, as having one copy of the HbS variant (also known as having sickle cell trait) provides significant protection against severe malaria. 2 (See sidebar “History of the HbS variant.”)
23andMe’s updated Sickle Cell Anemia report can now inform customers with two copies of the HbS variant that they are at risk of developing symptoms of sickle cell anemia. These customers will also receive information about how their result may be relevant for their children and for other relatives.
In 2018, scientists published a genetic study analyzing the DNA of nearly 3,000 people to trace the genetic history of sickle cell anemia. They found that the HbS variant arose once, in sub-Saharan Africa, about 7,000 years ago. As people migrated to other parts of the world, the HbS variant became more common in places where malaria-carrying mosquitoes were common, because it provided significant protection against severe malaria. Reference: Shriner D et al. (2018). “Whole-Genome-Sequence-Based Haplotypes Reveal Single Origin of the Sickle Allele during the Holocene Wet Phase.” Am J Hum Genet. 102(4):547-556. [https://pubmed.ncbi.nlm.nih.gov/29526279/]
How sickle cell anemia is inherited
In order to have sickle cell anemia, a person must inherit two copies of the HbS variant — one from each biological parent. People with just one copy of the HbS variant are called carriers; they’re also said to have sickle cell trait. They’re not expected to have sickle cell anemia themselves, and they typically do not experience any health complications. But they could pass their variant on to their future children. If their partner has the HbS variant or another variant in the HBB gene, there’s a 25 percent chance that each child may have sickle cell anemia or a related blood disorder. (See sidebar “Other Types of Sickle Cell Disease.”)
Why it’s important to learn about sickle cell anemia
About 1 in 13 African Americans and ~300 million people worldwide are carriers for sickle cell anemia. 2, 3 But individual and community awareness of sickle cell anemia and how it’s inherited is often limited.
For example, although all 50 U.S. states include newborn screenings for sickle cell trait and sickle cell disease, many people with sickle cell trait do not know their status, in part because it’s up to individual state health departments to follow up with those families, leading to variability in who receives their results, how they are notified, and how much follow-up education and counseling is provided. 4 5, 6,7, 8, 9, 10 There are also common misunderstandings about how sickle cell anemia is inherited, the distinction between sickle cell trait and sickle cell anemia, and how common it is to be a carrier. 11, 12, 13, 14
In addition to sickle cell anemia, there are other types of sickle cell disease caused by variants in the HBB gene. Instead of having two copies of the HbS variant like people with sickle cell anemia, people with other types of sickle cell disease have one copy of the HbS variant and one copy of another variant in the HBB gene. Examples of other types of sickle cell disease include hemoglobin SC disease and sickle beta thalassemia disease.
In addition, sickle cell anemia is often thought to be a condition that primarily impacts people with African ancestry. But the HbS variant is found around the world, including in people with ancestry from the Middle East, South Asia, the Mediterranean region of Europe, and parts of Central and South America.1,15 For this reason, the American College of Medical Genetics and Genomics (ACMG) and the American College of Obstetricians and Gynecologists (ACOG) recently updated their carrier screening guidelines to recommend that people of all ethnicities who are considering having children should be offered carrier screening for hemoglobinopathies such as sickle cell anemia.16, 17 Previously, most guidelines only recommended this type of screening for people of certain ancestries.
Actionable health information
Knowing if you’re a carrier for sickle cell anemia — or for another type of sickle cell disease caused by variants in the HBB gene — can be important in family planning. In addition to providing information that may be important for reproductive decision-making, carrier testing can help parents to plan for the birth of a child with the condition, and can prompt cascade testing of family members who may also have the same variant.
People with one copy of the HbS variant may also have another variant in the HBB gene, so it’s important that they talk to a healthcare professional about additional testing. In addition, in rare cases carriers for sickle cell anemia may experience some health impacts. You can learn more about sickle cell trait from the CDC and the American Society of Hematology.
In addition to the Sickle Cell Anemia Carrier Status report — which can help people learn whether they are a carrier for sickle cell anemia and explore information about the health risks associated with the condition — 23andMe is working on other projects to raise awareness and improve our understanding of sickle cell anemia and sickle cell trait. For example, we have worked with the Breaking the SSickle Cell Cycle Foundation on an awareness campaign to increase access to sickle cell trait information, promote sickle cell disease awareness, and offer resources for individuals with sickle cell trait and sickle cell disease.
Our Research team is also working with collaborators at Johns Hopkins University School of Medicine and the National Human Genome Research Institute to investigate potential health risks associated with having sickle cell trait.
Want to learn more?
The updated Sickle Cell Anemia Carrier Status report is available to 23andMe Health + Ancestry Service customers. Customers with two copies of the HbS variant who were genotyped after November 2013 will now receive information about their risk of developing symptoms of sickle cell anemia. Customers on all genotyping platforms can learn whether they are carriers for the HbS variant.
Acknowledgements: We are incredibly grateful to the following individuals for their valuable input on the updated report: Rakhi P. Naik, MD, MHS, Johns Hopkins University School of Medicine; Dr. Lametra Scott, Breaking the SSickle Cell Cycle Foundation; Dr. Herman Taylor, Dr. Tennille Leak-Johnson, and Dr. Jason Payne from the Morehouse School of Medicine; and Jacquelyn George, MPH, Jeanette Nu’Man, MEd, and Kadeem Harrison from the Sickle Cell Foundation of Georgia. We also thank the 23andMe employees who worked to make this update possible. This includes members of the Product R&D, Medical Affairs, Research, Regulatory, Quality Assurance, Engineering, Legal, Customer Care, Product, Marketing, and Communications teams who contributed to the development and release of the report, as well as the members of 23andMe’s Sickle Cell Carrier Status Awareness Program core team.
*The 23andMe PGS test uses qualitative genotyping to detect select clinically relevant variants in the genomic DNA of adults for the purpose of reporting carrier status and reporting and interpreting genetic health risks. The relevance of each report may vary based on ethnicity. Our carrier status reports can be used to determine carrier status, but cannot determine if you have two copies of any genetic variant. These carrier reports are not intended to tell you anything about your risk for developing a disease in the future or anything about the health of your fetus, or your newborn child’s risk of developing a particular disease later in life. For certain conditions, we provide a single report that includes information on both carrier status and genetic health risk. The Sickle Cell Anemia carrier status report is indicated for the detection of the HbS variant in the HBB gene. The report can tell you if you have two copies of the tested variant, and if you are at risk of developing symptoms of sickle cell anemia, but does not describe your overall risk of developing symptoms. This test is most relevant for people of African descent. It is also relevant for people of Middle Eastern and South Asian descent, as well as people from the Caribbean, the Mediterranean, and parts of Central and South America.
References
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[2] Centers for Disease Control and Prevention. “Data & Statistics on Sickle Cell Disease.” Retrieved Sep 16, 2022, from https://www.cdc.gov/ncbddd/sicklecell/data.html [https://www.cdc.gov/ncbddd/sicklecell/data.html]
[3] Cleveland Clinic. “Sickle Cell Disease.” Retrieved Jan 6, 2023, from https://my.clevelandclinic.org/health/diseases/12100-sickle-cell-disease [https://my.clevelandclinic.org/health/diseases/12100-sickle-cell-disease]
[4] Harrison SE et al. (2017). “Knowledge and Awareness of Sickle Cell Trait Among Young African American Adults.” West J Nurs Res. 39(9):1222-1239. [https://pubmed.ncbi.nlm.nih.gov/27550467/]
[5] Kavanagh PL et al. (2008). “Communication of positive newborn screening results for sickle cell disease and sickle cell trait: variation across states.” Am J Med Genet C Semin Med Genet. 148C(1):15-22. [https://pubmed.ncbi.nlm.nih.gov/18200513/]
[6] El-Haj N et al. (2018). “Newborn Screening for SCD in the USA and Canada.” Int J Neonatal Screen. 4(4):36. [https://pubmed.ncbi.nlm.nih.gov/33072956/]
[7] La Pean A et al. (2012). “A qualitative secondary evaluation of statewide follow-up interviews for abnormal newborn screening results for cystic fibrosis and sickle cell hemoglobinopathy.” Genet Med. 14(2):207-14. [https://pubmed.ncbi.nlm.nih.gov/22261754/]
[8] Creary S et al. (2017). “Sickle cell trait knowledge and health literacy in caregivers who receive in-person sickle cell trait education.” Mol Genet Genomic Med. 5(6):692-699. [https://pubmed.ncbi.nlm.nih.gov/29178654/]
[9] Moseley KL et al. (2013). “Who counsels parents of newborns who are carriers of sickle cell anemia or cystic fibrosis?” J Genet Couns. 22(2):218-25. [https://pubmed.ncbi.nlm.nih.gov/22903793/]
[10] “The current state of sickle cell trait: implications for reproductive and genetic counseling.” Hematology Am Soc Hematol Educ Program. 2018(1):474-481. [https://pubmed.ncbi.nlm.nih.gov/30504348/]
[11] Treadwell MJ et al. (2006). “Using qualitative and quantitative strategies to evaluate knowledge and perceptions about sickle cell disease and sickle cell trait.” J Natl Med Assoc. 98(5):704-10. [https://pubmed.ncbi.nlm.nih.gov/16749645/]
[12] Acharya K et al. (2009). “A pilot study to explore knowledge, attitudes, and beliefs about sickle cell trait and disease.” J Natl Med Assoc. 101(11):1163-72. [https://pubmed.ncbi.nlm.nih.gov/19998646/]
[13] Gustafson SL et al. (2007). “Health beliefs among African American women regarding genetic testing and counseling for sickle cell disease.” Genet Med. 9(5):303-10. [https://pubmed.ncbi.nlm.nih.gov/17505208/]
[14] Long KA et al. (2011). “Attitudes and beliefs of African-Americans toward genetics, genetic testing, and sickle cell disease education and awareness.” J Genet Couns. 20(6):572-92. [https://pubmed.ncbi.nlm.nih.gov/21748660/]
[15] Piel FB et al. (2013). “Global epidemiology of sickle haemoglobin in neonates: a contemporary geostatistical model-based map and population estimates.” Lancet. 381(9861):142-51. [https://www.ncbi.nlm.nih.gov/pubmed/23103089]
[16] Gregg AR et al. (2021). “Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).” Genet Med. 23(10):81793-1806. [https://pubmed.ncbi.nlm.nih.gov/34285390/]
[17] American College of Obstetricians and Gynecologists. (2022). “Practice Advisory: Hemoglobinopathies in Pregnancy.” Retrieved Oct 11, 2022, from https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy [https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2022/08/hemoglobinopathies-in-pregnancy]
