@article {459, title = {Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people}, journal = {Proceedings of the National Academy of Sciences (PNAS)}, volume = {119}, year = {2022}, pages = {e2202764119}, abstract = {

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80\% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 \× 10\−8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26\% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

}, keywords = {genome-wide association study, language, meta-analysis, reading}, doi = {10.1073/pnas.2202764119}, author = {Eising, Else and Mirza-Schreiber, Nazanin and de Zeeuw, Eveline L and Wang, Carol A and Truong, Dongnhu T and Allegrini, Andrea G and Shapland, Chin Yang and Zhu, Gu and Wigg, Karen G and Gerritse, Margot L and Molz, Barbara and Alag{\"o}z, G{\"o}kberk and Gialluisi, Alessandro and Abbondanza, Filippo and Rimfeld, Kaili and van Donkelaar, Marjolein and Liao, Zhijie and Jansen, Philip R and Andlauer, Till F M and Bates, Timothy C and Bernard, Manon and Blokland, Kirsten and Bonte, Milene and B{\o}rglum, Anders D and Bourgeron, Thomas and Brandeis, Daniel and Ceroni, Fabiola and Cs{\'e}pe, Val{\'e}ria and Dale, Philip S and de Jong, Peter F and DeFries, John C and D{\'e}monet, Jean-Fran\c cois and Demontis, Ditte and Feng, Yu and Gordon, Scott D and Guger, Sharon L and Hayiou-Thomas, Marianna E and Hern{\'a}ndez-Cabrera, Juan A and Hottenga, Jouke-Jan and Hulme, Charles and Kere, Juha and Kerr, Elizabeth N and Koomar, Tanner and Landerl, Karin and Leonard, Gabriel T and Lovett, Maureen W and Lyytinen, Heikki and Martin, Nicholas G and Martinelli, Angela and Maurer, Urs and Michaelson, Jacob J and Moll, Kristina and Monaco, Anthony P and Morgan, Angela T and N{\"o}then, Markus M and Pausova, Zdenka and Pennell, Craig E and Pennington, Bruce F and Price, Kaitlyn M and Rajagopal, Veera M and Ramus, Franck and Richer, Louis and Simpson, Nuala H and Smith, Shelley D and Snowling, Margaret J and Stein, John and Strug, Lisa J and Talcott, Joel B and Tiemeier, Henning and van der Schroeff, Marc P and Verhoef, Ellen and Watkins, Kate E and Wilkinson, Margaret and Wright, Margaret J and Barr, Cathy L and Boomsma, Dorret I and Carreiras, Manuel and Franken, Marie-Christine J and Gruen, Jeffrey R and Luciano, Michelle and M{\"u}ller-Myhsok, Bertram and Newbury, Dianne F and Olson, Richard K and Paracchini, Silvia and Paus, Tom{\'a}\v s and Plomin, Robert and Reilly, Sheena and Schulte-K{\"o}rne, Gerd and Tomblin, J Bruce and van Bergen, Elsje and Whitehouse, Andrew J O and Willcutt, Erik G and St Pourcain, Beate and Francks, Clyde and Fisher, Simon E} } @article {409, title = {Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight}, journal = {Nature Communications}, volume = {10}, year = {2019}, pages = {1893}, abstract = {

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from \−183 to 178 grams per 10\% increase in methylation (PBonferroni\ \<\ 1.06\ x\ 10\−7). In additional analyses in 7,278 participants, \<1.3\% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood.\ Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p\ = 6.12\ x\ 10\−74) and BMI in pregnancy (3/914, p = 1.13x10\−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

}, doi = {10.1038/s41467-019-09671-3}, author = {K{\"u}pers, Leanne K and Monnereau, Claire and Sharp, Gemma C and Yousefi, Paul and Salas, Lucas A and Ghantous, Akram and Page, Christian M and Reese, Sarah E and Wilcox, Allen J and Czamara, Darina and Starling, Anne P and Novoloaca, Alexei and Lent, Samantha and Roy, Ritu and Hoyo, Cathrine and Breton, Carrie V and Allard, Catherine and Just, Allan C and Bakulski, Kelly M and Holloway, John W and Everson, Todd M and Xu, Cheng-Jian and Huang, Rae-Chi and van der Plaat, Diana A and Wielscher, Matthias and Merid, Simon Kebede and Ullemar, Vilhelmina and Rezwan, Faisal I and Lahti, Jari and van Dongen, Jenny and Langie, Sabine A S and Richardson, Tom G and Magnus, Maria C and Nohr, Ellen A and Xu, Zongli and Duijts, Liesbeth and Zhao, Shanshan and Zhang, Weiming and Plusquin, Michelle and DeMeo, Dawn L and Solomon, Olivia and Heimovaara, Joosje H and Jima, Dereje D and Gao, Lu and Bustamante, Mariona and Perron, Patrice and Wright, Robert O and Hertz-Picciotto, Irva and Zhang, Hongmei and Karagas, Margaret R and Gehring, Ulrike and Marsit, Carmen J and Beilin, Lawrence J and Vonk, Judith M and Jarvelin, Marjo-Riitta and Bergstr{\"o}m, Anna and {\"O}rtqvist, Anne K and Ewart, Susan and Villa, Pia M and Moore, Sophie E and Willemsen, Gonneke and Standaert, Arnout R L and H\aaberg, Siri E and S{\o}rensen, Thorkild I A and Taylor, Jack A and R{\"a}ikk{\"o}nen, Katri and Yang, Ivana V and Kechris, Katerina and Nawrot, Tim S and Silver, Matt J and Gong, Yun Yun and Richiardi, Lorenzo and Kogevinas, Manolis and Litonjua, Augusto A and Eskenazi, Brenda and Huen, Karen and Mbarek, Hamdi and Maguire, Rachel L and Dwyer, Terence and Vrijheid, Martine and Bouchard, Luigi and Baccarelli, Andrea A and Croen, Lisa A and Karmaus, Wilfried and Anderson, Denise and de Vries, Maaike and Sebert, Sylvain and Kere, Juha and Karlsson, Robert and Arshad, Syed Hasan and H{\"a}m{\"a}l{\"a}inen, Esa and Routledge, Michael N and Boomsma, Dorret I and Feinberg, Andrew P and Newschaffer, Craig J and Govarts, Eva and Moisse, Matthieu and Fallin, M Daniele and Mel{\'e}n, Erik and Prentice, Andrew M and Kajantie, Eero and Almqvist, Catarina and Oken, Emily and Dabelea, Dana and Boezen, H Marike and Melton, Phillip E and Wright, Rosalind J and Koppelman, Gerard H and Trevisi, Letizia and Hivert, Marie-France and Sunyer, Jordi and Munthe-Kaas, Monica C and Murphy, Susan K and Corpeleijn, Eva and Wiemels, Joseph and Holland, Nina and Herceg, Zdenko and Binder, Elisabeth B and Davey Smith, George and Jaddoe, Vincent W V and Lie, Rolv T and Nystad, Wenche and London, Stephanie J and Lawlor, Debbie A and Relton, Caroline L and Snieder, Harold and Felix, Janine F} }