Higher Vitamin D-binding protein is good (neonates in this case) – Feb 2023

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Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots

.Nat Commun 2023 Feb 15;14(1):852. doi: 10.1038/s41467-023-36392-5.

Clara Albiñana 1, Zhihong Zhu 1, Nis Borbye-Lorenzen 2, Sanne Grundvad Boelt 2 3, Arieh S Cohen 4, Kristin Skogstrand 2, Naomi R Wray 5 6, Joana A Revez 5, Florian Privé 1, Liselotte V Petersen 1 7, Cynthia M Bulik 8 9 10, Oleguer Plana-Ripoll 1 11, Katherine L Musliner 12, Esben Agerbo 1 7 13, Anders D Børglum 7 14 15, David M Hougaard 7 16, Merete Nordentoft 7 17 18, Thomas Werge 7 19 20 21, Preben Bo Mortensen 1 7 13, Bjarni J Vilhjálmsson 1 7 22, John J McGrath 23 24 25

The Vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the Vitamin D_system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of Vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on Vitamin D status and a range of health outcomes.
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Grant support
na/Danmarks Grundforskningsfond (Danish National Research Foundation)
R345-2020-1588/Lundbeckfonden (Lundbeck Foundation)
R102-A9118, R155-2014-1724, and R248-2017-2003/Lundbeckfonden (Lundbeck Foundation)
R276-2018-4581/Lundbeckfonden (Lundbeck Foundation)
R335-2019-2339/Lundbeckfonden (Lundbeck Foundation)

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VitaminDWiki – Vitamin D Binding Protein category listing has 178 items and the following introduction

Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,

• GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
• The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
• The actual D getting to the cells is a function of measured D and all 4 genes
• There is >2X increase in 8+ health problems if have poor VDBP (GC)
• It appears that VDBP only blocks oral vitamin D,
  • but NOT Vitamin D from sun, UV, topical or inhaled (tissue activated)
  • A clue: - Vitamin D from UV is 2X better for MS than oral Vitamin D

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VitaminDWiki – Vitamin D Binding Protein has a list of health problems

Increased Risk	Health Problem
11 X	Preeclampsia
6.5X	T1D in SA Blacks
6 X	Food Allergy
5 X	PTSD
4 X, 5X	Kidney Cancer
4 X	Poor Response to Oral Vitamin D
3 X	Ear infection
2.8 X	MS
2.5 X	Severe Autism
2 X	Colorectal Cancer
2 X	Prostate Cancer -in those with dark skins
1.3 X	Infertility

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VitaminDWiki - Genetics chart shows the vitamin D genes

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Study references

1. Bouillon, R., Schuit, F., Antonio, L. & Rastinejad, F. Vitamin D binding protein: a historic overview. Front. Endocrinol. 10, 910 (2019). - DOI
2. Chun, R. F. New perspectives on the Vitamin D binding protein. Cell Biochem. Funct. 30, 445–456 (2012). - PubMed - DOIing
3. Mendel, C. M. The free hormone hypothesis: a physiologically based mathematical model. Endocr. Rev. 10, 232–274 (1989). - PubMed - DOI
4. Bikle, D. D. & Schwartz, J. Vitamin D binding protein, total and free Vitamin D levels in different physiological and pathophysiological conditions. Front. Endocrinol. 10, 317 (2019). - DOI
5. Henderson, C. M. et al. Vitamin D-binding protein deficiency and homozygous deletion of the GC gene. N. Engl. J. Med. 380, 1150–1157 (2019). - PubMed - PMC - DOI
6. Zella, L. A., Shevde, N. K., Hollis, B. W., Cooke, N. E. & Pike, J. W. Vitamin D-binding protein influences total circulating levels of 1,25-dihydroxyvitamin D3 but does not directly modulate the bioactive levels of the hormone in vivo. Endocrinology 149, 3656–3667 (2008). - PubMed - PMC - DOI
7. Berg, A. H. et al. Development and analytical validation of a novel bioavailable 25-hydroxyVitamin D assay. PLoS ONE 16, e0254158 (2021). - PubMed - PMC - DOI
8. Denburg, M. R. et al. Comparison of two ELISA methods and mass spectrometry for measurement of vitamin D-binding protein: implications for the assessment of bioavailable Vitamin D concentrations across genotypes. J. Bone Miner. Res. 31, 1128–1136 (2016). - PubMed - DOI
9. Moy, K. A. et al. Genome-wide association study of circulating vitamin D-binding protein. Am. J. Clin. Nutr. 99, 1424–1431 (2014). - PubMed - PMC - DOI
10. Ahn, J. et al. Genome-wide association study of circulating Vitamin D levels. Hum. Mol. Genet. https://doi.org/10.1093/hmg/ddq155 (2010).
11. Revez, J. A. et al. Genome-wide association study identifies 143 loci associated with 25 hydroxyVitamin D concentration. Nat. Commun. 11, 1647 (2020). - PubMed - PMC - DOI
12. Wang, T. J. et al. Common genetic determinants of Vitamin D insufficiency: a genome-wide association study. Lancet 376, 180–188 (2010). - PubMed - PMC - DOI
13. Manousaki, D. et al. Genome-wide association study for Vitamin D Levels reveals 69 independent loci. Am. J. Hum. Genet. 106, 327–337 (2020). - PubMed - PMC - DOI
14. Pludowski, P. et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun. Rev. 12, 976–989 (2013). - PubMed - DOI
15. Holick, M. F. & Chen, T. C. Vitamin D deficiency: a worldwide problem with health consequences. Am. J. Clin. Nutr. 87, 1080S–1086S (2008). - PubMed - DOI
16. Holick, M. F. Vitamin D deficiency. N. Engl. J. Med. 357, 266–281 (2007). - PubMed - DOI
17. Eyles, D. W. et al. The association between neonatal Vitamin D status and risk of schizophrenia. Sci. Rep. 8, 17692 (2018). - PubMed - PMC - DOI
18. McGrath, J. J. et al. Neonatal Vitamin D status and risk of schizophrenia: a population-based case-control study. Arch. Gen. Psychiatry 67, 889–894 (2010). - PubMed - DOI
19. Ronaldson, A. et al. Prospective associations between Vitamin D and depression in middle-aged adults: findings from the UK Biobank cohort. Psychol. Med. https://doi.org/10.1017/s0033291720003657 (2020).
20. Cereda, G., Enrico, P., Ciappolino, V., Delvecchio, G. & Brambilla, P. The role of Vitamin D in bipolar disorder: epidemiology and influence on disease activity. J. Affect. Disord. 278, 209–217 (2021). - PubMed - DOI
21. Lee, B. K. et al. Developmental Vitamin D and autism spectrum disorders: findings from the Stockholm Youth Cohort. Mol. Psychiatry 26, 1578–1588 (2021). - PubMed - DOI
22. Sourander, A. et al. Maternal Vitamin D levels during pregnancy and offspring autism spectrum disorder. Biol. Psychiatry 90, 790–797 (2021). - PubMed - PMC - DOI
23. Wang, Z., Ding, R. & Wang, J. The association between Vitamin D status and autism spectrum disorder (ASD): a systematic review and meta-analysis. Nutrients https://doi.org/10.3390/nu13010086 (2020).
24. Vinkhuyzen, A. A. E. et al. Gestational Vitamin D deficiency and autism-related traits: the Generation R Study. Mol. Psychiatry 23, 240–246 (2018). - PubMed - DOI
25. Vinkhuyzen, A. A. E. et al. Gestational Vitamin D deficiency and autism spectrum disorder. BJPsych Open 3, 85–90 (2017). - PubMed - PMC - DOI
26. Sucksdorff, M. et al. Maternal Vitamin D levels and the risk of offspring attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 60, 142–151 e142 (2021). - PubMed - DOI
27. Mossin, M. H. et al. Inverse associations between cord Vitamin D and attention deficit hyperactivity disorder symptoms: a child cohort study. Aust. N. Z. J. Psychiatry 51, 703–710 (2017). - PubMed - DOI
28. Navale, S. S., Mulugeta, A., Zhou, A., Llewellyn, D. J. & Hypponen, E. Vitamin D and brain health: an observational and Mendelian randomization study. Am. J. Clin. Nutr. 116, 531–540 (2022). - PubMed - PMC - DOI
29. Balion, C. et al. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 79, 1397–1405 (2012). - PubMed - PMC - DOI
30. Xia, K. et al. Dietary-derived essential nutrients and amyotrophic lateral sclerosis: a two-sample Mendelian randomization study. Nutrients https://doi.org/10.3390/nu14050920 (2022).
31. Jiang, X., Ge, T. & Chen, C. Y. The causal role of circulating Vitamin D concentrations in human complex traits and diseases: a large-scale Mendelian randomization study. Sci. Rep. 11, 184 (2021). - PubMed - PMC - DOI
32. Nielsen, N. M. et al. Neonatal Vitamin D status and risk of multiple sclerosis: a population-based case-control study. Neurology 88, 44–51 (2017). - PubMed - PMC - DOI
33. Hahn, J. et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 376, e066452 (2022). - PubMed - PMC - DOI
34. Lemieux, P. et al. Effects of 6-month Vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial. Eur. J. Endocrinol. 181, 287–299 (2019). - PubMed - DOI
35. Fletcher, J., Cooper, S. C., Ghosh, S. & Hewison, M. The role of Vitamin D in inflammatory bowel disease: mechanism to management. Nutrients https://doi.org/10.3390/nu11051019 (2019).
36. Zou, J., Thornton, C., Chambers, E. S., Rosser, E. C. & Ciurtin, C. Exploring the evidence for an immunomodulatory role of Vitamin D in juvenile and adult rheumatic disease. Front. Immunol. 11, 616483 (2020). - PubMed - DOI
37. Pedersen, C. B. et al. The iPSYCH2012 case-cohort sample: new directions for unravelling genetic and environmental architectures of severe mental disorders. Mol. Psychiatry 23, 6–14 (2018). - PubMed - DOI
38. Pendergrass, S. A. et al. The use of phenome-wide association studies (PheWAS) for exploration of novel genotype-phenotype relationships and pleiotropy discovery. Genet. Epidemiol. 35, 410–422 (2011). - PubMed - PMC - DOI
39. Amrein, K. et al. Vitamin D deficiency 2.0: an update on the current status worldwide. Eur. J. Clin. Nutr. 74, 1498–1513 (2020). - PubMed - PMC - DOI
40. Keller, A. et al. Concentration of 25-hydroxyVitamin D from neonatal dried blood spots and the relation to gestational age, birth weight and Ponderal Index: the D-tect study. Br. J. Nutr. 119, 1416–1423 (2018). - PubMed - DOI
41. Zaitlen, N. et al. Using extended genealogy to estimate components of heritability for 23 quantitative and dichotomous traits. PLoS Genet. 9, e1003520 (2013). - PubMed - PMC - DOI
42. Weissbrod, O. et al. Functionally informed fine-mapping and polygenic localization of complex trait heritability. Nat. Genet. 52, 1355–1363 (2020). - PubMed - PMC - DOI
43. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D (National Academies Press, 2010).
44. Ashley, B. et al. Placental uptake and metabolism of 25(OH)Vitamin D determine its activity within the fetoplacental unit. Elife https://doi.org/10.7554/eLife.71094 (2022).
45. Auburger, G. et al. 12q24 locus association with type 1 diabetes: SH2B3 or ATXN2? World J. Diabetes 5, 316–327 (2014). - PubMed - PMC - DOI
46. Liu, X., Xia, S., Zhang, Z., Wu, H. & Lieberman, J. Channelling inflammation: gasdermins in physiology and disease. Nat. Rev. Drug Discov. 20, 384–405 (2021). - PubMed - PMC - DOI
47. Bjorkhem-Bergman, L., Torefalk, E., Ekstrom, L. & Bergman, P. Vitamin D binding protein is not affected by high-dose Vitamin D supplementation: a post hoc analysis of a randomised, placebo-controlled study. BMC Res. Notes 11, 619 (2018). - PubMed - PMC - DOI
48. Chun, R. F. et al. Vitamin D and DBP: the free hormone hypothesis revisited. J. Steroid Biochem. Mol. Biol. 144 Pt A, 132–137 (2014). - PubMed - DOI
49. Banerjee, R. R. et al. Very low Vitamin D in a patient with a novel pathogenic variant in the GC gene that encodes vitamin D-binding protein. J. Endocr. Soc. 5, bvab104 (2021). - PubMed - PMC - DOI
50. Jones, K. S. et al. 25(OH)D2 half-life is shorter than 25(OH)D3 half-life and is influenced by DBP concentration and genotype. J. Clin. Endocrinol. Metab. 99, 3373–3381 (2014). - PubMed - PMC - DOI
51. Karras, S. N., Koufakis, T., Fakhoury, H. & Kotsa, K. Deconvoluting the biological roles of vitamin D-binding protein during pregnancy: a both clinical and theoretical challenge. Front. Endocrinol. 9, 259 (2018). - DOI
52. Zhang, J. Y., Lucey, A. J., Horgan, R., Kenny, L. C. & Kiely, M. Impact of pregnancy on Vitamin D status: a longitudinal study. Br. J. Nutr. 112, 1081–1087 (2014). - PubMed - DOI
53. Harroud, A. & Richards, J. B. Mendelian randomization in multiple sclerosis: a causal role for Vitamin D and obesity? Mult. Scler. 24, 80–85 (2018). - PubMed - DOI
54. Manousaki, D. et al. Low-frequency synonymous coding variation in CYP2R1 has large effects on Vitamin D levels and risk of multiple sclerosis. Am. J. Hum. Genet. 101, 227–238 (2017). - PubMed - PMC - DOI
55. Rhead, B. et al. Mendelian randomization shows a causal effect of low Vitamin D on multiple sclerosis risk. Neurol. Genet. 2, e97 (2016). - PubMed - PMC - DOI
56. Mokry, L. E. et al. Vitamin D and risk of multiple sclerosis: a Mendelian randomization study. PLoS Med. 12, e1001866 (2015). - PubMed - PMC - DOI
57. Deluca, G. C., Kimball, S. M., Kolasinski, J., Ramagopalan, S. V. & Ebers, G. C. The role of Vitamin D in nervous system health and disease. Neuropathol. Appl. Neurobiol. https://doi.org/10.1111/nan.12020 (2013).
58. Cutolo, M., Otsa, K., Uprus, M., Paolino, S. & Seriolo, B. Vitamin D in rheumatoid arthritis. Autoimmun. Rev. 7, 59–64 (2007). - PubMed - DOI
59. Merlino, L. A. et al. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum. 50, 72–77 (2004). - PubMed - DOI
60. Hewison, M. Vitamin D and the immune system. J. Endocrinol. 132, 173–175 (1992). - PubMed - DOI
61. Xie, Z., Wang, X. & Bikle, D. D. Editorial: Vitamin D binding protein, total and free Vitamin D levels in different physiological and pathophysiological conditions. Front. Endocrinol. 11, 40 (2020). - DOI
62. Jassil, N. K., Sharma, A., Bikle, D. & Wang, X. Vitamin D binding protein and 25-hydroxyVitamin D levels: emerging clinical applications. Endocr. Pract. 23, 605–613 (2017). - PubMed - PMC - DOI
63. Nielson, C. M. et al. Free 25-hydroxyvitamin D: impact of Vitamin D binding protein assays on racial-genotypic associations. J. Clin. Endocrinol. Metab. 101, 2226–2234 (2016). - PubMed - PMC - DOI
64. Powe, C. E. et al. Vitamin D-binding protein and Vitamin D status of black Americans and white Americans. N. Engl. J. Med. 369, 1991–2000 (2013). - PubMed - PMC - DOI
65. Hollis, B. W. & Bikle, D. D. Vitamin D–binding protein and Vitamin D in Blacks and Whites. N. Engl. J. Med. 370, 878–881 (2014).
66. Alzaman, N. S., Dawson-Hughes, B., Nelson, J., D’Alessio, D. & Pittas, A. G. Vitamin D status of black and white Americans and changes in Vitamin D metabolites after varied doses of Vitamin D supplementation. Am. J. Clin. Nutr. 104, 205–214 (2016). - PubMed - PMC - DOI
67. Pietzner, M. et al. Mapping the proteo-genomic convergence of human diseases. Science 374, eabj1541 (2021). - PubMed - PMC - DOI
68. Ferkingstad, E. et al. Large-scale integration of the plasma proteome with genetics and disease. Nat. Genet. 53, 1712–1721 (2021). - PubMed - DOI
69. Buniello, A. et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 47, D1005–D1012 (2019). - PubMed - DOI
70. Kronenberg, F. et al. Influence of hematocrit on the measurement of lipoproteins demonstrated by the example of lipoprotein(a). Kidney Int. 54, 1385–1389 (1998). - PubMed - DOI
71. Hall, E. M., Flores, S. R. & De Jesus, V. R. Influence of hematocrit and total-spot volume on performance characteristics of dried blood spots for newborn screening. Int J. Neonatal Screen 1, 69–78 (2015). - PubMed - DOI
72. Thornton, L. M. et al. The anorexia nervosa genetics initiative (ANGI): overview and methods. Contemp. Clin. Trials 74, 61–69 (2018). - PubMed - PMC - DOI
73. Norgaard-Pedersen, B. & Hougaard, D. M. Storage policies and use of the Danish Newborn Screening Biobank. J. Inherit. Metab. Dis. 30, 530–536 (2007). - PubMed - DOI
74. Hollegaard, M. V. et al. Whole genome amplification and genetic analysis after extraction of proteins from dried blood spots. Clin. Chem. 53, 1161–1162 (2007). - PubMed - DOI
75. Boelt, S. G. et al. Sensitive and robust LC-MS/MS assay to quantify 25-hydroxyVitamin D in leftover protein extract from dried blood spots. Int. J. Neonatal Screen. 7, 82 (2021). - PubMed - PMC - DOI
76. Boelt, S. G. et al. A method to correct for the influence of bovine serum albumin-associated Vitamin D metabolites in protein extracts from neonatal dried blood spots. BMC Res. Notes 15, 194 (2022). - PubMed - PMC - DOI
77. Eyles, D. W. et al. The utility of neonatal dried blood spots for the assessment of neonatal Vitamin D status. Paediatr. Perinat. Epidemiol. 24, 303–308 (2010). - PubMed - DOI
78. Eyles, D. et al. A sensitive LC/MS/MS assay of 25OH vitamin D3 and 25OH vitamin D2 in dried blood spots. Clin. Chim. Acta 403, 145–151 (2009). - PubMed - DOI
79. Kvaskoff, D. et al. Minimizing matrix effects for the accurate quantification of 25-hydroxyVitamin D metabolites in dried blood spots by LC-MS/MS. Clin. Chem. 62, 639–646 (2016). - PubMed - DOI
80. Kvaskoff, D., Ko, P., Simila, H. A. & Eyles, D. W. Distribution of 25-hydroxyvitamin D3 in dried blood spots and implications for its quantitation by tandem mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 901, 47–52 (2012). - DOI
81. Carter, G. D. et al. HydroxyVitamin D assays: an historical perspective from DEQAS. J. Steroid Biochem. Mol. Biol. 177, 30–35 (2018). - PubMed - DOI
82. McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279–1283 (2016). - PubMed - PMC - DOI
83. Lam, M. et al. RICOPILI: rapid imputation for COnsortias PIpeLIne. Bioinformatics 36, 930–933 (2020). - PubMed - DOI
84. Prive, F., Luu, K., Blum, M. G. B., McGrath, J. J. & Vilhjalmsson, B. J. Efficient toolkit implementing best practices for principal component analysis of population genetic data. Bioinformatics 36, 4449–4457 (2020). - PubMed - PMC - DOI
85. Prive, F. et al. Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort. Am. J. Hum. Genet. 109, 12–23 (2022). - PubMed - PMC - DOI
86. Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76–82 (2011). - PubMed - PMC - DOI
87. Jiang, L. et al. A resource-efficient tool for mixed model association analysis of large-scale data. Nat. Genet. 51, 1749–1755 (2019). - PubMed - DOI
88. Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44, 369–375 (2012). S361-363. - PubMed - PMC - DOI
89. Zhu, Z. et al. Causal associations between risk factors and common diseases inferred from GWAS summary data. Nat. Commun. 9, 224 (2018). - PubMed - PMC - DOI
90. Yengo, L. et al. Meta-analysis of genome-wide association studies for height and body mass index in approximately 700000 individuals of European ancestry. Hum. Mol. Genet. 27, 3641–3649 (2018). - PubMed - PMC - DOI
91. Bulik-Sullivan, B. K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291–295 (2015). - PubMed - PMC - DOI
92. Zeng, J. et al. Widespread signatures of natural selection across human complex traits and functional genomic categories. Nat. Commun. 12, 1164 (2021). - PubMed - PMC - DOI
93. Privé, F., Arbel, J. & Vilhjálmsson, B. J. LDpred2: better, faster, stronger. Bioinformatics 36, 5424–5431 (2020). - PubMed - PMC - DOI
94. Zou, Y., Carbonetto, P., Wang, G. & Stephens, M. Fine-mapping from summary data with the “Sum of Single Effects” model. PLoS Genet. 18, e1010299 (2022).
95. Gazal, S. et al. Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 1421–1427 (2017). - PubMed - PMC - DOI
96. McLaren, W. et al. The Ensembl variant effect predictor. Genome Biol. 17, 122 (2016). - PubMed - PMC - DOI
97. Lloyd-Jones, L. R. et al. Improved polygenic prediction by Bayesian multiple regression on summary statistics. Nat. Commun. 10, 5086 (2019). - PubMed - PMC - DOI
98. Lambert, S. A. et al. The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation. Nat. Genet. 53, 420–425 (2021). - PubMed - DOI
99. Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015). - PubMed - PMC - DOI
100. Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017). - PubMed - PMC - DOI
101. Trubetskoy, V. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604, 502–508 (2022). - PubMed - PMC - DOI
102. Howard, D. M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat. Neurosci. 22, 343–352 (2019). - PubMed - PMC - DOI
103. Mullins, N. et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat. Genet. 53, 817–829 (2021). - PubMed - PMC - DOI
104. Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431–444 (2019). - PubMed - PMC - DOI
105. Demontis, D. et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat. Genet. 51, 63–75 (2019). - PubMed - DOI
106. Marioni, R. E. et al. GWAS on family history of Alzheimer’s disease. Transl. Psychiatry 8, 99 (2018). - PubMed - PMC - DOI
107. Okbay, A. et al. Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. Nat. Genet. 54, 437–449 (2022). - PubMed - PMC - DOI
108. International Multiple Sclerosis Genetics, C. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science https://doi.org/10.1126/science.aav7188 (2019).
109. van Rheenen, W. et al. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat. Genet. 53, 1636–1648 (2021). - PubMed - PMC - DOI
110. Chiou, J. et al. Interpreting type 1 diabetes risk with genetics and single-cell epigenomics. Nature 594, 398–402 (2021). - PubMed - DOI
111. de Lange, K. M. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 49, 256–261 (2017). - PubMed - PMC - DOI
112. Okada, Y. et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 506, 376–381 (2014). - PubMed - DOI
113. GTEx Consortium. Genetic effects on gene expression across human tissues. Nature 550, 204 (2017). - PMC - DOI