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Polygenic score

A polygenic score is a concept in genetics. It is a number which adds up different aspects of a person as shown by their genetics. Bear in mind that is is now possible to have a very complete sequence of a person's genetic material (roughly, genes).[1][2][3]

Polygenic scores are usually created from large scientific studies that look at the DNA of many people. These are called genome-wide association studies (GWASs). They can find out how important certain variants are. "Effect" is the name for the importance of a variant. Polygenic scores are made by adding up the effects of a large number of genetic variants. These genetic variants are known as alleles or SNPs.[4][5][6]

It is used to estimate how likely a person is to have a trait or disease. It suggests how likely a person is to, for example, suffer a disease or disability as a result of their genetics.[7][8][9][10][11] A polygenic score is the effect of many genetic variants on a trait. Polygenic scores can also tell how much of a trait or disease someone will have.[12][13][14][15][16]

Polygenic scores can be used in adult humans. Polygenic scores are also sometimes used to decide if embryos are likely to have a disease.

Uses

Polygenic scores can make prediction of disease better. They help to know who will get the disease.[17] Polygenic scores tell something new about a person's risk for a disease. This means that polygenic scores can be useful even if there are other already known risks.[18] For example, a risk for lung cancer is smoking and a risk for heart disease is obesity. Some risks for diseases are only possible to know later in someone's life. However, polygenic scores can be made at the very beginning of someone's life.[19] This way, polygenic scores can help to know someone's risk for disease earlier on.[20] Some people have polygenic scores that say they are at high risk for a disease. These people can be helped earlier so they are less likely to get a disease.[21]

 
Monogenic testing only looks at one gene at a time. Polygenic testing can look any many genes across the entire genome.

Polygenic scores are very useful for diseases involving the heart, or blood. Some of the names of these diseases are coronary artery disease (plaque in the heart), hypertension (high blood pressure), atrial fibrillation (not-normal heartbeat), cerebrovascular disease (problems with blood in the brain).[17] This means polygenic scores may be useful in diseases related to the heart, or diseases related to metabolism (how the body uses food). Polygenic scores can help find people who are at risk of coronary artery disease (plaque staying inside the arteries near the heart) even if their family members don't have it.[22]

Hyperlipidemia is when there are too many fats in the blood. It is a condition that happens when there is a lot of cholesterol and triglycerides (lipids) in someone's blood. Polygenic scores can help to know a person's risk of getting hyperlipidemia. Polygenic scores might also help a doctor treat a person who already has hyperlipidemia.[23] Someone who has family members with hyperlipidemia has less risk of getting hyperlipidemia if their polygenic score says that they have low risk.[24]

ADHD is a disorder where someone has hyperactivity or issues with attention. There are polygenic scores for ADHD. These scores are related to if someone will be diagnosed with ADHD. These scores are also related to how severe their ADHD is. Polygenic scores for ADHD might help find which children have ADHD earlier in their lives.[25]

Polygenic scores are good at predicting if someone will get Alzheimer's disease or not.[26][27] Polygenic scores for Alzheimer's disease can help determine if the hippocampus, a part of the brain, will get smaller.[26]

Some polygenic scores tell about, or predict, cognitive ability and how many years someone has gone to school.[28][29][19]

Some other polygenic scores have been made, such as for schizophrenia, depression, bipolar disorder, neuroticism, externalizing behaviors, extraversion, and anxiety.[28][29][30]

Polygenic scores are used commonly in animal breeding and plant breeding. They help improve livestock and crops.[31]

Polygenic scores are also used to see if embryos are at risk of developing various diseases. This lets parents choose the baby that will be the healthiest.[32]

Making polygenic scores

Polygenic scores are made by finding lots of people who have a disease, and lots of people who do not. The DNA of these people is studied. Scientists see if DNA variations happen more in the people with the disease, or happen less in the people with the disease. This figures out which DNA variations, or genes, are important. Because some of these DNA variations are more important than others, the more important DNA variations affect the polygenic score more. Often, very big groups of people[33] are used to make polygenic scores. One of these big groups of people is the UK Biobank.[34]

Populations sometimes have different frequencies of genes. Before making a polygenic score, the data is changed so that genes that are different between populations will not affect the results.[35] Scientists can use different ways of making polygenic scores more accurate. They choose to not use very correlated DNA variations that are close together, to avoid counting the same DNA variation twice. They can include only the DNA variations that they are sure of, or they can include even DNA variations that they are not sure of. They can use machine learning to do this better. They can also use DNA variations about traits related to the trait or disease that they are studying, in order to have more data.[36][37]

Polygenic Score Media

  • An illustration of the distribution and stratification ability of a polygenic risk score. The left panel shows how in the predictions of disease risk, the PRS on the x-axis, can separate cases (i.e.

  • An early (2006) example of a genetic risk score applied to Type 2 Diabetes in humans. Individuals with Type 2 diabetes (white bars) have a higher score than controls (black bars).

  • Predicted vs actual height using a polygenic risk score

References

  1. ↑ Dudbridge F (March 2013). "Power and predictive accuracy of polygenic risk scores". PLOS Genetics. 9 (3): e1003348. doi:10.1371/journal.pgen.1003348. PMC 3605113. PMID 23555274.
  2. ↑ Torkamani A, Wineinger NE, Topol EJ (September 2018). "The personal and clinical utility of polygenic risk scores". Nature Reviews. Genetics. 19 (9): 581–590. doi:10.1038/s41576-018-0018-x. PMID 29789686. S2CID 46893131.
  3. ↑ Lambert SA, Abraham G, Inouye M (November 2019). "Towards clinical utility of polygenic risk scores". Human Molecular Genetics. 28 (R2): R133–R142. doi:10.1093/hmg/ddz187. PMID 31363735.
  4. ↑ Dudbridge F (March 2013). "Power and predictive accuracy of polygenic risk scores". PLOS Genetics. 9 (3): e1003348. doi:10.1371/journal.pgen.1003348. PMC 3605113. PMID 23555274.
  5. ↑ Torkamani A, Wineinger NE, Topol EJ (September 2018). "The personal and clinical utility of polygenic risk scores". Nature Reviews. Genetics. 19 (9): 581–590. doi:10.1038/s41576-018-0018-x. PMID 29789686. S2CID 46893131.
  6. ↑ Lambert SA, Abraham G, Inouye M (November 2019). "Towards clinical utility of polygenic risk scores". Human Molecular Genetics. 28 (R2): R133–R142. doi:10.1093/hmg/ddz187. PMID 31363735.
  7. ↑ de Vlaming R, Groenen PJ (2015). "The Current and Future Use of Ridge Regression for Prediction in Quantitative Genetics". BioMed Research International. 2015: 143712. doi:10.1155/2015/143712. PMC 4529984. PMID 26273586.
  8. ↑ Lewis CM, Vassos E (November 2017). "Prospects for using risk scores in polygenic medicine". Genome Medicine. 9 (1): 96. doi:10.1186/s13073-017-0489-y. PMC 5683372. PMID 29132412.
  9. ↑ Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. (September 2018). "Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations". Nature Genetics. 50 (9): 1219–1224. doi:10.1038/s41588-018-0183-z. PMC 6128408. PMID 30104762.
  10. ↑ Yanes T, Meiser B, Kaur R, Scheepers-Joynt M, McInerny S, Taylor S, et al. (March 2020). "Uptake of polygenic risk information among women at increased risk of breast cancer". Clinical Genetics. 97 (3): 492–501. doi:10.1111/cge.13687. hdl:11343/286783. PMID 31833054. S2CID 209342044.
  11. ↑ Vilhjálmsson BJ, Yang J, Finucane HK, Gusev A, Lindström S, Ripke S, et al. (October 2015). "Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores". American Journal of Human Genetics. 97 (4): 576–592. doi:10.1016/j.ajhg.2015.09.001. PMC 4596916. PMID 26430803.
  12. ↑ de Vlaming R, Groenen PJ (2015). "The Current and Future Use of Ridge Regression for Prediction in Quantitative Genetics". BioMed Research International. 2015: 143712. doi:10.1155/2015/143712. PMC 4529984. PMID 26273586.
  13. ↑ Lewis CM, Vassos E (November 2017). "Prospects for using risk scores in polygenic medicine". Genome Medicine. 9 (1): 96. doi:10.1186/s13073-017-0489-y. PMC 5683372. PMID 29132412.
  14. ↑ Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. (September 2018). "Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations". Nature Genetics. 50 (9): 1219–1224. doi:10.1038/s41588-018-0183-z. PMC 6128408. PMID 30104762.
  15. ↑ Yanes T, Meiser B, Kaur R, Scheepers-Joynt M, McInerny S, Taylor S, et al. (March 2020). "Uptake of polygenic risk information among women at increased risk of breast cancer". Clinical Genetics. 97 (3): 492–501. doi:10.1111/cge.13687. hdl:11343/286783. PMID 31833054. S2CID 209342044.
  16. ↑ Vilhjálmsson BJ, Yang J, Finucane HK, Gusev A, Lindström S, Ripke S, et al. (October 2015). "Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores". American Journal of Human Genetics. 97 (4): 576–592. doi:10.1016/j.ajhg.2015.09.001. PMC 4596916. PMID 26430803.
  17. ↑ 17.0 17.1 Phulka, Jobanjit S.; Ashraf, Mishal; Bajwa, Beenu K.; Pare, Guillaume; Laksman, Zachary (2023). "Current State and Future of Polygenic Risk Scores in Cardiometabolic Disease: A Scoping Review". Circulation. Genomic and Precision Medicine. 16 (3): 286–313. doi:10.1161/CIRCGEN.122.003834. ISSN 2574-8300. PMID 37035923.
  18. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74 (1): 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 0066-4219. Polygenic scores capture risk information that is largely independent of traditional risk factors.
  19. ↑ 19.0 19.1 Plomin, Robert; von Stumm, Sophie (2018). "The new genetics of intelligence". Nature Reviews Genetics. 19 (3): 148–159. doi:10.1038/nrg.2017.104. ISSN 1471-0064.
  20. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74 (1): 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 0066-4219. A key advantage of a polygenic score is that it can be assessed very early in life, before the onset of traditional risk factors.
  21. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74 (1): 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 0066-4219. Once a high-risk individual is identified based on their polygenic score, several studies have shown they may stand to benefit from preventive interventions.
  22. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74: 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 1545-326X. PMID 36315649.
  23. ↑ Dron, Jacqueline S. (2023-04-01). "The clinical utility of polygenic risk scores for combined hyperlipidemia". Current Opinion in Lipidology. 34 (2): 44–51. doi:10.1097/MOL.0000000000000865. ISSN 1473-6535. PMID 36602940.
  24. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74 (1): 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 0066-4219. Therefore, familial hypercholesterolemia variant carriers with polygenic scores in the lowest quintile are at a near-population-average CAD risk.
  25. ↑ Green, Allison; Baroud, Evelyne; DiSalvo, Maura; Faraone, Stephen V.; Biederman, Joseph (2022). "Examining the impact of ADHD polygenic risk scores on ADHD and associated outcomes: A systematic review and meta-analysis". Journal of Psychiatric Research. 155: 49–67. doi:10.1016/j.jpsychires.2022.07.032. ISSN 1879-1379. PMID 35988304.
  26. ↑ 26.0 26.1 Harrison, Judith R.; Mistry, Sumit; Muskett, Natalie; Escott-Price, Valentina (2020-01-01). "From Polygenic Scores to Precision Medicine in Alzheimer's Disease: A Systematic Review". Journal of Alzheimer's Disease. 74 (4): 1271–1283. doi:10.3233/JAD-191233. ISSN 1387-2877.
  27. ↑ Stocker, Hannah; Möllers, Tobias; Perna, Laura; Brenner, Hermann (2018-08-24). "The genetic risk of Alzheimer's disease beyond APOE ε4: systematic review of Alzheimer's genetic risk scores". Translational Psychiatry. 8 (1): 1–9. doi:10.1038/s41398-018-0221-8. ISSN 2158-3188.
  28. ↑ 28.0 28.1 Malanchini, Margherita; Rimfeld, Kaili; Allegrini, Andrea G.; Ritchie, Stuart J.; Plomin, Robert (2020-04-01). "Cognitive ability and education: How behavioural genetic research has advanced our knowledge and understanding of their association". Neuroscience & Biobehavioral Reviews. 111: 229–245. doi:10.1016/j.neubiorev.2020.01.016. ISSN 0149-7634.
  29. ↑ 29.0 29.1 Cite error: Invalid <ref> tag; no text was provided for refs named :2.
  30. ↑ Wray, Naomi R.; Lee, Sang Hong; Mehta, Divya; Vinkhuyzen, Anna A.E.; Dudbridge, Frank; Middeldorp, Christel M. (2014). "Research Review: Polygenic methods and their application to psychiatric traits". Journal of Child Psychology and Psychiatry. 55 (10): 1068–1087. doi:10.1111/jcpp.12295.
  31. ↑ Spindel JE, McCouch SR (December 2016). "When more is better: how data sharing would accelerate genomic selection of crop plants". The New Phytologist. 212 (4): 814–826. doi:10.1111/nph.14174. PMID 27716975.
  32. ↑ Kimelman, Dana; Pavone, Mary Ellen (2021-01-01). "Non-invasive prenatal testing in the context of IVF and PGT-A". Best Practice & Research Clinical Obstetrics & Gynaecology. Reproduction at an Advanced Maternal Age. 70: 51–62. doi:10.1016/j.bpobgyn.2020.07.004. ISSN 1521-6934.
  33. ↑ Plomin, Robert; von Stumm, Sophie (2022). "Polygenic scores: prediction versus explanation". Molecular Psychiatry. 27 (1): 49–52. doi:10.1038/s41380-021-01348-y. ISSN 1476-5578.
  34. ↑ Patel, Aniruddh P.; Khera, Amit V. (2023-01-27). "Advances and Applications of Polygenic Scores for Coronary Artery Disease". Annual Review of Medicine. 74: 141–154. doi:10.1146/annurev-med-042921-112629. ISSN 1545-326X. PMID 36315649.
  35. ↑ Plomin, Robert; von Stumm, Sophie (2022). "Polygenic scores: prediction versus explanation". Molecular Psychiatry. 27 (1): 49–52. doi:10.1038/s41380-021-01348-y. ISSN 1476-5578.
  36. ↑ Allegrini, Andrea G.; Baldwin, Jessie R.; Barkhuizen, Wikus; Pingault, Jean‐Baptiste (2022-10-01). "Research Review: A guide to computing and implementing polygenic scores in developmental research". Journal of Child Psychology and Psychiatry. 63 (10): 1111–1124. doi:10.1111/jcpp.13611. ISSN 0021-9630. PMC 10108570. PMID 35354222. {{cite journal}}: Check |pmc= value (help)
  37. ↑ Plomin, Robert; von Stumm, Sophie (2018). "The new genetics of intelligence". Nature Reviews Genetics. 19 (3): 148–159. doi:10.1038/nrg.2017.104. ISSN 1471-0064.
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