@article {144,
	title = {A cross-population atlas of genetic associations for 220 human phenotypes.},
	journal = {Nat Genet},
	volume = {53},
	year = {2021},
	month = {2021 10},
	pages = {1415-1424},
	abstract = {<p>Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (n = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.</p>},
	keywords = {ABO Blood-Group System, Biological Specimen Banks, Genetic Association Studies, Genetic Loci, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Major Histocompatibility Complex, Meta-Analysis as Topic, Mutation, Phenotype},
	issn = {1546-1718},
	doi = {10.1038/s41588-021-00931-x},
	author = {Sakaue, Saori and Kanai, Masahiro and Tanigawa, Yosuke and Karjalainen, Juha and Kurki, Mitja and Koshiba, Seizo and Narita, Akira and Konuma, Takahiro and Yamamoto, Kenichi and Akiyama, Masato and Ishigaki, Kazuyoshi and Suzuki, Akari and Suzuki, Ken and Obara, Wataru and Yamaji, Ken and Takahashi, Kazuhisa and Asai, Satoshi and Takahashi, Yasuo and Suzuki, Takao and Shinozaki, Nobuaki and Yamaguchi, Hiroki and Minami, Shiro and Murayama, Shigeo and Yoshimori, Kozo and Nagayama, Satoshi and Obata, Daisuke and Higashiyama, Masahiko and Masumoto, Akihide and Koretsune, Yukihiro and Ito, Kaoru and Terao, Chikashi and Yamauchi, Toshimasa and Komuro, Issei and Kadowaki, Takashi and Tamiya, Gen and Yamamoto, Masayuki and Nakamura, Yusuke and Kubo, Michiaki and Murakami, Yoshinori and Yamamoto, Kazuhiko and Kamatani, Yoichiro and Palotie, Aarno and Rivas, Manuel A and Daly, Mark J and Matsuda, Koichi and Okada, Yukinori}
}
@article {113,
	title = {Improving the trans-ancestry portability of polygenic risk scores by prioritizing variants in predicted cell-type-specific regulatory elements.},
	journal = {Nat Genet},
	volume = {52},
	year = {2020},
	month = {2020 12},
	pages = {1346-1354},
	abstract = {<p>Poor trans-ancestry portability of polygenic risk scores is a consequence of Eurocentric genetic studies and limited knowledge of shared causal variants. Leveraging regulatory annotations may improve portability by prioritizing functional over tagging variants. We constructed a resource of 707 cell-type-specific IMPACT regulatory annotations by aggregating 5,345 epigenetic datasets to predict binding patterns of 142 transcription factors across 245 cell types. We then partitioned the common SNP heritability of 111 genome-wide association study summary statistics of European (average n ≈ 189,000) and East Asian (average n ≈ 157,000) origin. IMPACT annotations captured consistent SNP heritability between populations, suggesting prioritization of shared functional variants. Variant prioritization using IMPACT resulted in increased trans-ancestry portability of polygenic risk scores from Europeans to East Asians across all 21 phenotypes analyzed (49.9\% mean relative increase in R). Our study identifies a crucial role for functional annotations such as IMPACT to improve the trans-ancestry portability of genetic data.</p>},
	keywords = {Asian Continental Ancestry Group, Base Sequence, Computational Biology, Enhancer Elements, Genetic, European Continental Ancestry Group, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Models, Genetic, Molecular Sequence Annotation, Multifactorial Inheritance, Polymorphism, Single Nucleotide},
	issn = {1546-1718},
	doi = {10.1038/s41588-020-00740-8},
	author = {Amariuta, Tiffany and Ishigaki, Kazuyoshi and Sugishita, Hiroki and Ohta, Tazro and Koido, Masaru and Dey, Kushal K and Matsuda, Koichi and Murakami, Yoshinori and Price, Alkes L and Kawakami, Eiryo and Terao, Chikashi and Raychaudhuri, Soumya}
}
