@article {455, title = {Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms}, journal = {Journal of the American Academy of Child \& Adolescent Psychiatry}, volume = {61}, year = {2022}, pages = {934{\textendash}945}, abstract = {

OBJECTIVE: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence.

METHOD: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.

RESULTS: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66\%, 95\% CI = 0.84-2.48

}, keywords = {anxiety, Depression, genetic epidemiology, molecular genetics, repeated measures}, doi = {10.1016/j.jaac.2021.11.035}, author = {Jami, Eshim S and Hammerschlag, Anke R and Ip, Hill F and Allegrini, Andrea G and Benyamin, Beben and Border, Richard and Diemer, Elizabeth W and Jiang, Chang and Karhunen, Ville and Lu, Yi and Lu, Qing and Mallard, Travis T and Mishra, Pashupati P and Nolte, Ilja M and Palviainen, Teemu and Peterson, Roseann E and Sallis, Hannah M and Shabalin, Andrey A and Tate, Ashley E and Thiering, Elisabeth and Vilor-Tejedor, Nat{\`a}lia and Wang, Carol and Zhou, Ang and Adkins, Daniel E and Alemany, Silvia and Ask, Helga and Chen, Qi and Corley, Robin P and Ehli, Erik A and Evans, Luke M and Havdahl, Alexandra and Hagenbeek, Fiona A and Hakulinen, Christian and Henders, Anjali K and Hottenga, Jouke Jan and Korhonen, Tellervo and Mamun, Abdullah and Marrington, Shelby and Neumann, Alexander and Rimfeld, Kaili and Rivadeneira, Fernando and Silberg, Judy L and van Beijsterveldt, Catharina E and Vuoksimaa, Eero and Whipp, Alyce M and Tong, Xiaoran and Andreassen, Ole A and Boomsma, Dorret I and Brown, Sandra A and Burt, S Alexandra and Copeland, William and Dick, Danielle M and Harden, K Paige and Harris, Kathleen Mullan and Hartman, Catharina A and Heinrich, Joachim and Hewitt, John K and Hopfer, Christian and Hypponen, Elina and Jarvelin, Marjo-Riitta and Kaprio, Jaakko and Keltikangas-J{\"a}rvinen, Liisa and Klump, Kelly L and Krauter, Kenneth and Kuja-Halkola, Ralf and Larsson, Henrik and Lehtim{\"a}ki, Terho and Lichtenstein, Paul and Lundstr{\"o}m, Sebastian and Maes, Hermine H and Magnus, Per and Munaf{\`o}, Marcus R and Najman, Jake M and Nj{\o}lstad, P\aal R and Oldehinkel, Albertine J and Pennell, Craig E and Plomin, Robert and Reichborn-Kjennerud, Ted and Reynolds, Chandra and Rose, Richard J and Smolen, Andrew and Snieder, Harold and Stallings, Michael and Standl, Marie and Sunyer, Jordi and Tiemeier, Henning and Wadsworth, Sally J and Wall, Tamara L and Whitehouse, Andrew J O and Williams, Gail M and Ystr{\o}m, Eivind and Nivard, Michel G and Bartels, Meike and Middeldorp, Christel M} } @article {461, title = {Item-level genome-wide association study of the Alcohol Use Disorders Identification Test in three population-based cohorts}, journal = {The American Journal of Psychiatry}, volume = {179}, year = {2022}, pages = {58{\textendash}70}, abstract = {

OBJECTIVE: Genome-wide association studies (GWASs) of the Alcohol Use Disorders Identification Test (AUDIT), a 10-item screen for alcohol use disorder (AUD), have elucidated novel loci for alcohol consumption and misuse. However, these studies also revealed that GWASs can be influenced by numerous biases (e.g., measurement error, selection bias), which may have led to inconsistent genetic correlations between alcohol involvement and AUD, as well as paradoxically negative genetic correlations between alcohol involvement and psychiatric disorders and/or medical conditions. The authors used genomic structural equation modeling to elucidate the genetics of alcohol consumption and problematic consequences of alcohol use as measured by AUDIT.

METHODS: To explore these unexpected differences in genetic correlations, the authors conducted the first item-level and the largest GWAS of AUDIT items (N=160,824) and applied a multivariate framework to mitigate previous biases.

RESULTS: The authors identified novel patterns of similarity (and dissimilarity) among the AUDIT items and found evidence of a correlated two-factor structure at the genetic level ({\textquoteleft}{\textquoteleft}consumption\&$\#$39;\&$\#$39; and {\textquoteleft}{\textquoteleft}problems,\&$\#$39;\&$\#$39; rg=0.80). Moreover, by applying empirically derived weights to each of the AUDIT items, the authors constructed an aggregate measure of alcohol consumption that was strongly associated with alcohol dependence (rg=0.67), moderately associated with several other psychiatric disorders, and no longer positively associated with health and positive socioeconomic outcomes. Lastly, by conducting polygenic analyses in three independent cohorts that differed in their ascertainment and prevalence of AUD, the authors identified novel genetic associations between alcohol consumption, alcohol misuse, and health.

CONCLUSIONS: This work further emphasizes the value of AUDIT for both clinical and genetic studies of AUD and the importance of using multivariate methods to study genetic associations that are more closely related to AUD.

}, keywords = {Alcohol, Alcohol Consumption, ALSPAC, Genomic Structural Equation Modeling, GWAS, Substance-Related and Addictive Disorders}, doi = {10.1176/appi.ajp.2020.20091390}, author = {Mallard, Travis T and Savage, Jeanne E and Johnson, Emma C and Huang, Yuye and Edwards, Alexis C and Hottenga, Jouke J and Grotzinger, Andrew D and Gustavson, Daniel E and Jennings, Mariela V and Anokhin, Andrey and Dick, Danielle M and Edenberg, Howard J and Kramer, John R and Lai, Dongbing and Meyers, Jacquelyn L and Pandey, Ashwini K and Harden, Kathryn Paige and Nivard, Michel G and de Geus, Eco J C and Boomsma, Dorret I and Agrawal, Arpana and Davis, Lea K and Clarke, Toni-Kim and Palmer, Abraham A and Sanchez-Roige, Sandra} } @article {435, title = {Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction}, journal = {Nature Genetics}, volume = {53}, year = {2021}, pages = {35{\textendash}44}, abstract = {

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57\% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success.

}, doi = {10.1038/s41588-020-00754-2}, author = {Demange, Perline A and Malanchini, Margherita and Mallard, Travis T and Biroli, Pietro and Cox, Simon R and Grotzinger, Andrew D and Tucker-Drob, Elliot M and Abdellaoui, Abdel and Arseneault, Louise and van Bergen, Elsje and Boomsma, Dorret I and Caspi, Avshalom and Corcoran, David L and Domingue, Benjamin W and Harris, Kathleen Mullan and Ip, Hill F and Mitchell, Colter and Moffitt, Terrie E and Poulton, Richie and Prinz, Joseph A and Sugden, Karen and Wertz, Jasmin and Williams, Benjamin S and de Zeeuw, Eveline L and Belsky, Daniel W and Harden, K Paige and Nivard, Michel G} }