What Exactly Do You Learn From Dna Testing For Genealogy

JAMA. Author manuscript; available in PMC 2021 Jun xiv.

Published in final edited form as:

PMCID: PMC8202415

NIHMSID: NIHMS1706174

Genetic Ancestry Testing What Is It and Why Is It Important?

Lynn B. Jorde

Department of Human Genetics, University of Utah School of Medicine, Table salt Lake Urban center

Michael J. Bamshad

Department of Pediatrics, Academy of Washington, Seattle.

Genetic ancestry testing. in which genetic data are used to approximate the geographic origins of a person'south contempo ancestors, has grown rapidly in popularity. A recent judge indicates that more than than 26 million people worldwide have undergone genetic ancestry testing past directly-to-consumer (DTC) companies.^one These tests provide information about an private'south ancestral roots, and they can help to connect people with their relatives, sometimes equally distantly related equally fourth or fifth cousins. Such data can be peculiarly useful when a person does non know their genealogical beginnings (eg. many adoptees and the descendants of forced migrants). Increasingly and not without controversy, genetic beginnings testing is being used beyond its original purpose, for example, to help identify or exclude criminal suspects.² In the clinical setting, persons may share their ancestry test results with their clinician with the expectation that the results will inform wellness care decisions.

How Information technology Works

Genetic beginnings testing involves the comparison of a large number of Dna variants measured in an individual with the frequencies of these variants in reference populations sampled from across the globe. The geographic region in which an private variant has its highest frequency is assumed to be the most likely location of an ancestor who transmitted the variant to the person being tested. Ancestry testing is traditionally done for mitochondrial Dna (transmitted only by females and reflecting the origin of 1 maternal ancestor) and for Y chromosome DNA (transmitted only from father to son and reflecting the origin of i paternal antecedent). A more comprehensive assessment of ancestry can be conducted by assaying a half meg or more autosomal variants (single-nucleotide variants [SNVs]; formerly single-nucleotide polymorphisms [SNPs]). which are inherited from both parents. Nigh usually, these SNVs are assayed using a Dna microarray, merely Dna sequence information can also be used. For autosomal testing, it is mutual to portray the most likely geographic origin of a group of SNVs located within a chromosome segment (eg, ancestry painting) (Effigy).^three By counting the percentage of SNVs originating from each geographic region, the per centum of an individual's beginnings derived from each region can be estimated.

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Estimates of Beginnings Composition

Breakdown of estimated percentages of beginnings from different worldwide populations ranked from highest to everyman and from continental to regional levels for one of the authors. Illustration adapted from results reported by 23andMe.

Beginnings can exist designated very broadly (eg, western Asian, southern European) or as finely equally past regions within individual countries. In the latter example, accuracy is probable to subtract, and some DTC companies allow the user correspondingly to adjust the degree of speculation in ancestral interpretation. In all cases, accuracy is strongly afflicted by the choice of reference populations and the option and number of SNVs, all of which vary among beginnings testing companies. Consequently, it is not unusual for different companies to study somewhat dissimilar ancestral profiles for the same Dna sample.^four Furthermore, many human being populations have migrated considerably during their history⁵; therefore, modern-day samples represent a static and potentially inaccurate portrayal of a region's inhabitants in the past. Even the term ancestry is discipline to a diversity of interpretations and can exist based on geographic, historical, cultural, or religious definitions.^half-dozen For these reasons, there is considerable room for mistake or ambiguity in inferring and interpreting a person's genetic ancestry. Nonetheless, some studies have shown concordance between self-reported and genetically estimated ancestry.⁷

Of import Clinical Intendance Considerations

Noesis of a person's beginnings can be important because the frequencies of genetic risk variants sometimes vary with beginnings, although most such risk variants are not assayed straight by ancestry tests. Nevertheless, some DTC ancestry testing companies provide health reports in which they directly test a limited number of Deoxyribonucleic acid variants associated with conditions such every bit breast cancer and Alzheimer illness or less common genetic weather such as cystic fibrosis, polycystic kidney disease, and various inborn errors of metabolism (the latter enabling identification of carrier condition).

In most genetic research studies of wellness and disease, beginnings data has replaced the use of racial categories. Considering of its increased accuracy in comparison with self-reported ancestry, genetically estimated ancestry tin amend statistical power to observe genetic run a risk factors for common diseases in genome-wide association studies.⁸ Often such take a chance factors vary by beginnings, and the cumulative disease risk aggregated across multiple Dna variants (ie, the polygenic risk score) appears to exist highly sensitive to differences in beginnings.⁹ Appropriately, if the clinical utility of polygenic risk scores is eventually established, ancestry data could be important for accurate interpretation of risk. Moreover, because the bully majority of genetic studies have been done in populations of European ancestry, the pathogenicity of rare variants is more than difficult to appraise in persons of predominantly not-European ancestry. Beginnings information can thus help to avert misinterpretation of genetic tests.

Beginnings testing likewise can yield unanticipated results such as lack of expected ancestry or the presence of unexpected ancestry. Discordance between pairs of siblings or between father and child tin can reveal nonpaternity, which is estimated to occur in approximately1% to 2% of births in Western populations.¹⁰ Large identical regions of Deoxyribonucleic acid on both chromosomes in a tested private can identify parental consanguinity. These results could accept significant psychosocial impacts.

Value

Ancestry information has interpretive value in both clinical and enquiry settings, and provides more authentic and personalized information about a patient's genetic heritage than do wide categories like race or ethnicity. For example, in a self-identified African American patient with recurrent respiratory infections, beginnings testing could reveal that both copies of the CFTR gene are likely to have a European origin, increasing the relative likelihood of a diagnosis of cystic fibrosis. Although DTC beginnings testing does not predict an individual's hereafter health, it is relatively inexpensive (approximately $100) and widely bachelor. If DTC delivery of wellness-related genetic test results gains acceptance, it is likely that ancestry testing companies volition add more variants of medical relevance to their platforms, and clinicians volition be expected to understand and explain these results.

Bear witness Base

The authors are enlightened of no clinical care guidelines regarding ancestry testing. In a clinical setting, beginnings information tin can be helpful for selecting the most advisable genetic test (eg, for rare genetic atmospheric condition), interpreting genetic test results, and assessing risk for common diseases. However, associations betwixt ancestry and disease are indirect, and measurement of beginnings is subject to error. Ancestry testing is unlikely to go part of routine clinical care of any major medical specialty, peculiarly if risk variants tin can exist tested directly, as is expected with advances in precision medicine.

Bottom Line

Genetic ancestry testing can provide insights on the geographic origins of an individual's ancestors, every bit well as some information that can assist in cess of risk for some heritable conditions. The accurateness of testing is express by the migrations and mixing of populations over time. Unexpected findings regarding bequeathed origins and family relationships can have psychosocial consequences.

Footnotes

Disharmonize of Interest Disclosures: None reported.

Contributor Information

Lynn B. Jorde, Department of Human Genetics, University of Utah Schoolhouse of Medicine, Table salt Lake Urban center.

Michael J. Bamshad, Department of Pediatrics, University of Washington, Seattle.

REFERENCES

two. Phillips C Forensic genetic analysis of bio-geographical ancestry. Forensic Sci Int Genet. 2015;18:49–65. doi:10.1016/j.fsigen.2015.05.012 [PubMed] [CrossRef] [Google Scholar]

iii. Callaway E Ancestry testing goes for pinpoint accuracy. Nature. 2012;486(7401):17. doi:10.1038/486017a [PubMed] [CrossRef] [Google Scholar]

iv. Huml AM, Sullivan C, Figueroa Thou, Scott K, Sehgal AR. Consistency of direct-to-consumer genetic testing results among identical twins. Am J Med. 2019;133(1):143–146.e2. doi:10.1016/j.amjmed.2019.04.052 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

v. Hellenthal Thousand, Busby GBJ. Band G et al. A genetic atlas of human being admixture history. Science. 2014;343(6172):747–751. doi:ten.1126/science.1243518 [PMC free commodity] [PubMed] [CrossRef] [Google Scholar]

6. Royal CD, Novembre J, Fullerton SM, et al. Inferring genetic ancestry: opportunities, challenges, and implications. Am J Hum Genet. 2010;86(five):661–673. doi:10.1016/j.ajhg.2010.03.011 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

vii. Banda Y, Kvale MN, Hoffmann TJ, et al. Characterizing race/ethnicity and genetic beginnings for 100 000 subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetics. 2015;200(four):1285–1295. doi:ten.1534/genetics.115.178616 [PMC costless article] [PubMed] [CrossRef] [Google Scholar]

eight. Guo X Rotter Jl. Genome-wide association studies. JAMA. 2019;322(17):1705–1706. doi:10.1001/jama.2019.16479 [PubMed] [CrossRef] [Google Scholar]

nine. Sugrue LP, Desikan RS. What are polygenic scores and why are they important? JAMA. 2019;321(18):1820–1821. doi:x.1001/jama.2019.3893 [PubMed] [CrossRef] [Google Scholar]

x. Larmuseau MHD, Matthijs Thousand, Wenseleers T. Cuckolded fathers rare in human populations. Trends Ecol Evol. 2016;31(5):327–329. doi:10.1016/j.tree.2016.03.004 [PubMed] [CrossRef] [Google Scholar]