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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

23andMe Research Team, James J. Lee, COGENT (Cognitive Genomics Consortium)

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Social Science Genetic Association Consortium, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chanwook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal N. Timshel, Raymond K. Walters, Emily A. Willoughby, Loïc Yengo, Maris Alver, Yanchun Bao, David W. Clark, Felix R. Day, Nicholas A. Furlotte, Peter K. Joshi, Kathryn E. Kemper, Aaron Kleinman, Claudia Langenberg, Reedik Mägi, Joey W. Trampush, Shefali Setia Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Jason D. Boardman, Harry Campbell, Jeremy Freese, Kathleen Mullan Harris, Caroline Hayward, Pamela Herd, Meena Kumari, Todd Lencz, Jian’an Luan, Anil K. Malhotra, Andres Metspalu, Lili Milani, Ken K. Ong, John R. B. Perry, David J. Porteous, Marylyn D. Ritchie, Melissa C. Smart, Blair H. Smith, Joyce Y. Tung, Nicholas J. Wareham, James F. Wilson, Jonathan P. Beauchamp, Dalton C. Conley, Tõnu Esko, Steven F. Lehrer, Patrik K. E. Magnusson, Sven Oskarsson, Tune H. Pers, Matthew R. Robinson, Kevin Thom, Chelsea Watson, Christopher F. Chabris, Michelle N. Meyer, David I. Laibson, Jian Yang, Magnus Johannesson, Philipp D. Koellinger, Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini

2018 · Nature Genetics

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Original HN comments, with labels from simple text rules. A label describes the whole comment and may miss context or irony. Read the discussion to make up your own mind. About the labels

5 selected excerpts · 5 total mentions

xyzzyz
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You completely misunderstand the part you quote. What Plomin is saying is not that genetic heritability accounts for only 2-3% of the variance, but rather the GPSs, that is, the polygenic scores. What that means is that we can now point to concrete genes that contribute to intelligence, and assign them weights that tell us the significance of this contribution. This means that this 2-3% figure is not about reality of genetic contribution to intelligence on the ground, but rather about our explicit understanding thereof in 2014, when this article was originally published. Since then, our polygenic scores have significantly improved: for example, Lee et al in 2018…
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constructed polygenic scores that describe 11-13% of variance, a significant improvement over 2-3% result Plomin cites. There are probably even better results now, as the progress in the area is quick. Of course, 11-13% is still short of 80%+ that we already know is determined by genes, but our explicit understanding is slowly getting there. Importantly, as we get there, the goalposts of critics are constantly shifting: when we couldn’t point out to specific genes, the entire notion of heritability was attacked. Now that we can, the alleged problems are with spurious correlations resulting from population stratification etc. Alas, the science moves forward, despite fierce opposition. https://www.nature.com/articles/s41588-018-0147-3 > The denialism here lies with those who wish to believe that intelligence is largely genetically determined, rather than socially and environmentally determined. I think your inability to distinguish between heritability and polygenic scores makes you thoroughly unqualified to make statements like that.
sanxiyn
Neutral mention · rule
Not any more. We literally have a predictive function that takes DNA sequence as input and returns intelligence-correlate as output. It is public and you can run it with a couple of lines of Python. https://www.nature.com/articles/s41588-018-0147-3
wycs
Neutral mention · rule
I sense this is a lost cause, but we can already predict ~10 percent of the variance in educational attainment with the genome alone. Once we get data sets with millions of genomes tagged with their donors IQ, this number will rise. If we can predict, say, 60% of the variance in IQ (based on the genome alone) will you change you mind? That is, what sort of data would change your mind? https://www.nature.com/articles/s41588-018-0147-3
iguy
Neutral mention · rule
In fact a little worse, right now: we can predict about 20% of the variance in IQ from brain shape [1] but only 10% from genes [2]. [1] https://authors.library.caltech.edu/87270/ [2] https://www.nature.com/articles/s41588-018-0147-3
rfinney
Neutral mention · rule
Top 20 snps sorted by pval (top best) for Cognitive Performance ( from excel spreadsheet from https://www.nature.com/articles/s41588-018-0147-3#Sec34 ) dbSNP Frequency Allele 1 Effect size https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=235... rs2352974 0.4875 -0.0319 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=190... rs1906252 0.4873 0.0307 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=131... rs13107325 0.0750 -0.0543 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=938... rs9384679 0.3717 -0.0282 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=312... rs3128341 0.2052…
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-0.0334 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=242... rs2426132 0.4576 0.0270 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=121... rs12128707 0.7333 -0.0303 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=117... rs11793831 0.4158 0.0269 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=148... rs148696809 0.8828 -0.0406 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=272... rs2726513 0.4069 -0.0261 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=124... rs12448902 0.6061 0.0260 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=374... rs3740422 0.3506 -0.0255 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=805... rs8054299 0.6834 -0.0256 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=111... rs11123820 0.6057 -0.0243 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=108... rs10874938 0.5103 0.0236 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=108... rs10875914 0.5993 -0.0237 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=189... rs1892419 0.7699 0.0276 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=655... rs6550835 0.3249 -0.0248 https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=116... rs11662271 0.4733 0.0232

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