title: Evaluation of transethnic fine mapping with population-specific and cosmopolitan imputation reference panels in diverse Asian populations.
abstract: There has been limited success in identifying causal variants underlying association signals observed in genome-wide association studies (GWAS). The use of 1000 Genomes Project (1KGP) allows the imputation to estimate the genetic information at untyped variants. However, long stretches of high linkage disequilibrium within the genome prevent us from differentiating between causal variants and perfect surrogates, thus limiting our ability to identify causal variants. Transethnic strategies have been proposed as a possible solution to mitigate this. However, these studies generally rely on imputing genotypes from multiple ancestries from 1KGP but not against population-specific reference panels. Here, we perform the first transethnic fine-mapping study across three Asian cohorts from diverse ancestries at the loci implicated with eye and blood lipid traits, using population-specific reference panels that have been generated by whole-genome sequencing samples from the same ancestry groups. Our study outlines several challenges faced in a fine-mapping exercise where one simply aims to meta-analyse existing GWAS that have been imputed against reference haplotypes from the 1KGP.
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.|Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.|Department of Ophthalmology, National University of Singapore, Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Kee-Seng
authors.initials: KS
authors.lastname: Chia
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Life Sciences Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Peter
authors.initials: P
authors.lastname: Little
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.|Department of Ophthalmology, National University of Singapore, Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.|Department of Ophthalmology, National University of Singapore, Singapore, Singapore.|Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.|Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Singapore.|Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.|Life Sciences Institute, National University of Singapore, Singapore, Singapore.|NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore, Singapore.|Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
mesh_terms: D044466:Asian People / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods* / Q000592:standards; D056426:Genetic Loci; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods* / Q000592:standards; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D012015:Reference Standards