Using Local and Global Genetic Correlation Approaches to Help Elucidate the Shared Genetic Etiology of Psychiatric and Substance Use Traits

Abstract

Recent years have brought substantial progress in understanding the genetic etiology of psychiatric disorders, substance use traits, and substance use disorders (SUDs) ( 1 Deak J.D. Johnson E.C. Genetics of substance use disorders: A review. Psychol Med. 2021; 51: 2189-2200 Crossref Scopus (11) Google Scholar , 2 Gelernter J. Polimanti R. Genetics of substance use disorders in the era of big data. Nat Rev Genet. 2021; 22: 712-729 Crossref Scopus (11) Google Scholar , 3 Jang S-K. Saunders G. Liu M. Jiang Y. Liu D.J. Vrieze S. Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder. Psychol Med. 2022; 52: 968-978 Crossref Scopus (19) Google Scholar , 4 Lee P.H. Yen-Chen A.F. Smoller J.W. Pleiotropy and cross-disorder genetics among psychiatric disorders. Biol Psychiatry. 2021; 89: 20-31 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ). Genome-wide association studies (GWASs) have benefited greatly from large-scale datasets generated across international consortia and mega-biobanks allowing for well-powered GWASs of many psychiatric and substance use traits. These efforts have resulted in the discovery of thousands of genetic loci that influence these traits, have helped researchers understand the genetic architecture and polygenicity across disorders, and have informed our knowledge of patterns of shared genetic influences—largely through the application of global genetic correlation approaches ( 1 Deak J.D. Johnson E.C. Genetics of substance use disorders: A review. Psychol Med. 2021; 51: 2189-2200 Crossref Scopus (11) Google Scholar , 2 Gelernter J. Polimanti R. Genetics of substance use disorders in the era of big data. Nat Rev Genet. 2021; 22: 712-729 Crossref Scopus (11) Google Scholar , 3 Jang S-K. Saunders G. Liu M. Jiang Y. Liu D.J. Vrieze S. Genetic correlation, pleiotropy, and causal associations between substance use and psychiatric disorder. Psychol Med. 2022; 52: 968-978 Crossref Scopus (19) Google Scholar , 4 Lee P.H. Yen-Chen A.F. Smoller J.W. Pleiotropy and cross-disorder genetics among psychiatric disorders. Biol Psychiatry. 2021; 89: 20-31 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar ). A Local Genetic Correlation Analysis Provides Biological Insights Into the Shared Genetic Architecture of Psychiatric and Substance Use PhenotypesBiological PsychiatryVol. 92Issue 7PreviewGlobal genetic correlation analysis has provided valuable insight into the shared genetic basis between psychiatric and substance use disorders. However, little is known about which regions disproportionately contribute to the global correlation. Full-Text PDF