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Martin, Alicia

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Martin

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Alicia

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Martin, Alicia
Author's Publications: search.filters.isAuthorOfPublication.86ea6c1b-ef84-455f-8cf3-82186e8615b6

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    Publication
    Comparative Genetic Architectures of Schizophrenia in East Asian and European Populations
    (Cold Spring Harbor Laboratory, 2018-10-17) Lam, Max; Chen, Chia-Yen; Li, Zhiqiang; Ma, Xixian; Gaspar, Helena; Ikeda, Masashi; Benyamin, Beben; Brown, Brielin C.; Liu, Ruize; Zhou, Wei; Guan, Lili; Kamatani, Yoichiro; Kim, Sung-Wan; Kubo, Michiaki; Kusumawardhani, Agung; Liu, Chih-Min; Ma, Hong; Periyasamy, Sathish; Takahashi, Atsushi; Wang, Qiang; Xu, Zhida; Yu, Hao; Zhu, Feng; Chen, Wei J.; Faraone, Stephen; Glatt, Stephen J.; He, Lin; Hyman, Steven E.; Hwu, Hai-Gwo; Li, Tao; McCarroll, Steven; Neale, Benjamin M.; Sklar, Pamela; Wildenauer, Dieter; Yu, Xin; Zhang, Dai; Mowry, Bryan; Lee, Jimmy; Holmans, Peter; Xu, Shuhua; Sullivan, Patrick F.; Ripke, Stephan; O’Donovan, Michael; Daly, Mark J.; Qin, Shengying; Sham, Pak; Iwata, Nakao; Hong, Kyung S.; Schwab, Sibylle G.; Yue, Weihua; Tsuang, Ming; Liu, Jianjun; Ma, Xiancang; Kahn, René S.; Shi, Yongyong; Huang, Hailiang; Martin, Alicia; Bryois, Julien
    Schizophrenia is a severe psychiatric disorder with a lifetime risk of about 1% world-wide. Most large schizophrenia genetic studies have studied people of primarily European ancestry, potentially missing important biological insights. Here we present a study of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide significant schizophrenia associations in 19 genetic loci. Over the genome, the common genetic variants that confer risk for schizophrenia have highly similar effects in those of East Asian and European ancestry (rg=0.98), indicating for the first time that the genetic basis of schizophrenia and its biology are broadly shared across these world populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries revealed 208 genome-wide significant schizophrenia associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping more precisely isolated schizophrenia causal alleles in 70% of these loci. Despite consistent genetic effects across populations, polygenic risk models trained in one population have reduced performance in the other, highlighting the importance of including all major ancestral groups with sufficient sample size to ensure the findings have maximum relevance for all populations.
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    Publication
    Fine-Scale Genetic Structure in Finland
    (Genetics Society of America, 2017) Kerminen, Sini; Havulinna, Aki S.; Hellenthal, Garrett; Martin, Alicia; Sarin, Antti-Pekka; Perola, Markus; Palotie, Aarno; Salomaa, Veikko; Daly, Mark; Ripatti, Samuli; Pirinen, Matti
    Coupling dense genotype data with new computational methods offers unprecedented opportunities for individual-level ancestry estimation once geographically precisely defined reference data sets become available. We study such a reference data set for Finland containing 2376 such individuals from the FINRISK Study survey of 1997 both of whose parents were born close to each other. This sampling strategy focuses on the population structure present in Finland before the 1950s. By using the recent haplotype-based methods ChromoPainter (CP) and FineSTRUCTURE (FS) we reveal a highly geographically clustered genetic structure in Finland and report its connections to the settlement history as well as to the current dialectal regions of the Finnish language. The main genetic division within Finland shows striking concordance with the 1323 borderline of the treaty of Nöteborg. In general, we detect genetic substructure throughout the country, which reflects stronger regional genetic differences in Finland compared to, for example, the UK, which in a similar analysis was dominated by a single unstructured population. We expect that similar population genetic reference data sets will become available for many more populations in the near future with important applications, for example, in forensic genetics and in genetic association studies. With this in mind, we report those extensions of the CP + FS approach that we found most useful in our analyses of the Finnish data.