Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power

Author(s):Show less -

Atkinson, Elizabeth G. ^{[1, 2, 3]} ; Maihofer, Adam X. ^[4] ; Kanai, Masahiro ^{[1, 2, 5, 3, 6]} ; Martin, Alicia R. ^{[1, 2, 3]} ; Karczewski, Konrad J. ^{[2, 3]} ; Santoro, Marcos L. ^{[7, 8, 2]} ; Ulirsch, Jacob C. ^{[1, 2, 9, 3]} ; Kamatani, Yoichiro ^[10] ; Okada, Yukinori ^{[5, 11, 12]} ; Finucane, Hilary K. ^{[1, 2, 3]} ; Koenen, Karestan C. ^{[13, 2]} ; Nievergelt, Caroline M. ^[4] ; Daly, Mark J. ^{[1, 2, 14, 3]} ; Neale, Benjamin M. ^{[2, 3]}

Affiliation:Show less -

^[1] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 - USA

^[2] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 - USA

^[3] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 - USA

^[4] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 - USA

^[5] Osaka Univ, Grad Sch Med, Dept Stat Genet, Suita, Osaka - Japan

^[6] Harvard Med Sch, Program Bioinformat & Integrat Genom, Boston, MA 94305 - USA

^[7] Univ Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo - Brazil

^[8] Univ Fed Sao Paulo, Dept Psiquiatria, Sao Paulo - Brazil

^[9] Harvard Med Sch, Program Biol & Biomed Sci, Boston, MA 02115 - USA

^[10] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, Lab Complex Trait Genom, Tokyo - Japan

^[11] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka - Japan

^[12] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Suita, Osaka - Japan

^[13] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA - USA

^[14] Univ Helsinki, Inst Mol Med Finland, Helsinki - Finland

• Document type: Journal article
• Source: Nature Genetics; v. 53, n. 2, p. 195+, FEB 2021.
• Web of Science Citations: 1

Abstract

Admixed populations are routinely excluded from genomic studies due to concerns over population structure. Here, we present a statistical framework and software package, Tractor, to facilitate the inclusion of admixed individuals in association studies by leveraging local ancestry. We test Tractor with simulated and empirical two-way admixed African-European cohorts. Tractor generates accurate ancestry-specific effect-size estimates and p values, can boost genome-wide association study (GWAS) power and improves the resolution of association signals. Using a local ancestry-aware regression model, we replicate known hits for blood lipids, discover novel hits missed by standard GWAS and localize signals closer to putative causal variants. (AU)

• FAPESP's process: 18/09328-2 - Evaluation of polygenic risk score performance and gene-environment interaction in an admixed Brazilian cohort
• Grantee: Marcos Leite Santoro
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor