{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T13:51:17Z","timestamp":1776952277752,"version":"3.51.4"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32 GM007454"],"award-info":[{"award-number":["T32 GM007454"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Whole genome sequence (WGS) data provides opportunities for comprehensive evaluation of variants that may influence complex traits. However, prioritizing the large number of variants, particularly those in non\u2010coding regions, is a challenge. Here we present an approach that uses pedigree\u2010based haplotyping to identify the risk haplotype and resulting set of prioritized variants in a region of interest (ROI) defined by identity\u2010by\u2010descent (IBD) sharing among familial cases. The approach is applicable for use in both a full range of pedigree sizes and for the full allele frequency spectrum of variants without the need for a large reference sample. By determining haplotype sharing among individuals with WGS data, we demonstrate the ability to accurately identify a risk haplotype and a strongly reduced list of potential risk alleles for a trait of interest along with the cases who carry the risk haplotype. This is important in the context of complex traits where the disease may be etiologically heterogeneous even within a single pedigree. Application to both simulated and real Alzheimer's disease family data shows that the approach leads to accurate risk\u2010haplotype identification with marked reduction in the number of potential trait\u2010associated variants. Simulation also shows that the approach provides accurate risk haplotypes in ROIs.<\/jats:p>","DOI":"10.1002\/gepi.70039","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T08:23:16Z","timestamp":1772958196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variant Prioritization by Pedigree\u2010Based Haplotyping"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-1059","authenticated-orcid":false,"given":"Rafael A.","family":"Nafikov","sequence":"first","affiliation":[{"name":"University of Washington Division of Medical Genetics Department of Medicine Seattle Washington, DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harkirat K.","family":"Sohi","sequence":"additional","affiliation":[{"name":"University of Washington Division of Medical Genetics Department of Medicine Seattle Washington, DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Alejandro Q.","family":"Nato","sequence":"additional","affiliation":[{"name":"University of Washington Division of Medical Genetics Department of Medicine Seattle Washington, DC USA"},{"name":"Marshall University Department of Biomedical Sciences Joan C. 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