Narrow-sense heritability estimation of complex traits using identity-by-descent information
Narrow-sense heritability estimation of complex traits using identity-by-descent information
ABSTRACT Heritability is a fundamental parameter in genetics. Traditional estimates based on family or twin studies can be biased due to shared environmental or non-additive genetic variance. Alternatively, those based on genotyped or imputed variants typically underestimate narrow-sense heritability contributed by rare or otherwise poorly-tagged causal variants. Identical-by-descent (IBD) segments of the genome share all variants between pairs of chromosomes except new mutations that have arisen since the last common ancestor. Therefore, relating phenotypic similarity to degree of IBD sharing among classically unrelated individuals is an appealing approach to estimating the near full additive genetic variance while avoiding biases that can occur when modeling close relatives. We applied an IBD-based approach (GREML-IBD) to estimate heritability in unrelated individuals using phenotypic simulation with thousands of whole genome sequences across a range of stratification, polygenicity levels, and the minor allele frequencies of causal variants (CVs). IBD-based heritability estimates were unbiased when using unrelated individuals, even for traits with extremely rare CVs, but stratification led to strong biases in IBD-based heritability estimates with poor precision. We used data on two traits in ~120,000 people from the UK Biobank to demonstrate that, depending on the trait and possible confounding environmental effects, GREML-IBD can be applied successfully to very large genetic datasets to infer the contribution of very rare variants lost using other methods. However, we observed apparent biases in this real data that were not predicted from our simulation, suggesting that more work may be required to understand factors that influence IBD-based estimates.
Sharp Kevin、Gilly Arthur、Kooperberg Charles、Koskinen Seppo、Kretzschmar Warren、Kwong Alan、McCarthy Mark I、Lee James C、Luo Yang、Levy Shawn、Branham Kari、Breen Gerome、Busonero Fabio、Campbell Harry、Abecasis Gon?alo、Anderson Carl A、Berndt Sonja、Boomsma Dorrett、Schlessinger David、Sidore Carlo、Small Kerrin、Smith George Davey、Melzer David、Sampson Matthew G、Mohlke Karen L、Nauck Matthias、Nickerson Deborah、Palotie Aarno、Pirastu Nicola、Richards J Brent、Salomaa Veikko、Peters Ulrike、Zhang He、Wood Andrew R、Goddard Michael E.、Cocca Massimiliano、Collins Francis S、Corbin Laura J、Danecek Petr、Forer Lukas、Frayling Timothy、Fuchsberger Christian、Gandin Ilaria、Holmen Oddgeir L、Iacono William、Khalili Hamed、Tuomilehto Jaakko、Stambolian Dwight、Swaroop Anand、Swertz Morris A、Timpson Nicholas、Veldink Jan、Vrieze Scott、Wijmenga Cisca、Willer Cristen、Fraser Ross M、Jones Matthew、Dedoussis George、Das Sayantan、de Bakker Paul I W、Dorr Marcus、Durbin Richard、Farmaki Aliki-Eleni、Ripatti Samuli、Chew Emily、Tahmasbi Rasool、deCandia Teresa R.、Chan Andrew、Spector Timothy、Hveem Kristian、Soranzo Nicole、Chen Sai、Keller Matthew C.、Joshi Amit、Brummett Chad M、Traglia Michela、Delaneau Olivier、Das Sayantan、Sala Cinzia、Rheenen Wouter Van、Pato Michele、Marchini Jonathan、Yang Jian、Myers Richard M、McCarthy Shane、Campbell Peter、Walter Klaudia、Visscher Peter M.、Mezzavilla Massimo、Dekker Annelot、Gasparini Paolo、Altshuler David、Angius Andrea、Tuke Marcus、Hattersley Andrew、Teumer Alexander、den Berg Leonard H Van、McCarroll Steven、Pato Carlos、Schoenherr Sebastian、Vincent John B、Cucca Francesco、McInnis Melvin、Schoen Robert E、Toniolo Daniela、Gabriel Stacey、Vrieze Scott I.、Gillies Christopher E、Groop Leif、Kang Hyun Min、Abecasis Gon?alo R.、Scott Laura J、Boehnke Michael、Kretzler Matthias、Bjelland Doug W.、van Duijn Cornelia M、Barrett Jeffrey C、Slagboom P Eline、McGue Matt、Harrison Tabitha、Meitinger Thomas、Min Josine L、Evans Luke M.、- Haplotype Reference Consortium、Wilson James F、Volker Uwe、Mahajan Anubha、Ferrucci Luigi、Zeggini Eleftheria
Faculty of Veterinary and Agricultural Science, University of Melbourne||Biosciences Research, Department of Economic Development, Jobs, Transport and ResourcesDepartment of Psychology and Neuroscience, University of ColoradoInstitute for Behavioral Genetics, University of ColoradoInstitute for Behavioral Genetics, University of ColoradoInstitute for Behavioral Genetics, University of Colorado||Department of Psychology and Neuroscience, University of ColoradoCenter for Statistical Genetics, Department of Biostatistics, University of MichiganInstitute for Molecular Bioscience and the Queensland Brain Institute, University of QueenslandInstitute for Molecular Bioscience and the Queensland Brain Institute, University of QueenslandInstitute for Behavioral Genetics, University of ColoradoCenter for Statistical Genetics, Department of Biostatistics, University of MichiganInstitute for Behavioral Genetics, University of ColoradoInstitute for Behavioral Genetics, University of Colorado
遗传学生物科学理论、生物科学方法
Identical-by-descentIBDheritabilitymissing heritabilityGCTAshared haplotype
Sharp Kevin,Gilly Arthur,Kooperberg Charles,Koskinen Seppo,Kretzschmar Warren,Kwong Alan,McCarthy Mark I,Lee James C,Luo Yang,Levy Shawn,Branham Kari,Breen Gerome,Busonero Fabio,Campbell Harry,Abecasis Gon?alo,Anderson Carl A,Berndt Sonja,Boomsma Dorrett,Schlessinger David,Sidore Carlo,Small Kerrin,Smith George Davey,Melzer David,Sampson Matthew G,Mohlke Karen L,Nauck Matthias,Nickerson Deborah,Palotie Aarno,Pirastu Nicola,Richards J Brent,Salomaa Veikko,Peters Ulrike,Zhang He,Wood Andrew R,Goddard Michael E.,Cocca Massimiliano,Collins Francis S,Corbin Laura J,Danecek Petr,Forer Lukas,Frayling Timothy,Fuchsberger Christian,Gandin Ilaria,Holmen Oddgeir L,Iacono William,Khalili Hamed,Tuomilehto Jaakko,Stambolian Dwight,Swaroop Anand,Swertz Morris A,Timpson Nicholas,Veldink Jan,Vrieze Scott,Wijmenga Cisca,Willer Cristen,Fraser Ross M,Jones Matthew,Dedoussis George,Das Sayantan,de Bakker Paul I W,Dorr Marcus,Durbin Richard,Farmaki Aliki-Eleni,Ripatti Samuli,Chew Emily,Tahmasbi Rasool,deCandia Teresa R.,Chan Andrew,Spector Timothy,Hveem Kristian,Soranzo Nicole,Chen Sai,Keller Matthew C.,Joshi Amit,Brummett Chad M,Traglia Michela,Delaneau Olivier,Das Sayantan,Sala Cinzia,Rheenen Wouter Van,Pato Michele,Marchini Jonathan,Yang Jian,Myers Richard M,McCarthy Shane,Campbell Peter,Walter Klaudia,Visscher Peter M.,Mezzavilla Massimo,Dekker Annelot,Gasparini Paolo,Altshuler David,Angius Andrea,Tuke Marcus,Hattersley Andrew,Teumer Alexander,den Berg Leonard H Van,McCarroll Steven,Pato Carlos,Schoenherr Sebastian,Vincent John B,Cucca Francesco,McInnis Melvin,Schoen Robert E,Toniolo Daniela,Gabriel Stacey,Vrieze Scott I.,Gillies Christopher E,Groop Leif,Kang Hyun Min,Abecasis Gon?alo R.,Scott Laura J,Boehnke Michael,Kretzler Matthias,Bjelland Doug W.,van Duijn Cornelia M,Barrett Jeffrey C,Slagboom P Eline,McGue Matt,Harrison Tabitha,Meitinger Thomas,Min Josine L,Evans Luke M.,- Haplotype Reference Consortium,Wilson James F,Volker Uwe,Mahajan Anubha,Ferrucci Luigi,Zeggini Eleftheria.Narrow-sense heritability estimation of complex traits using identity-by-descent information[EB/OL].(2025-03-28)[2025-06-10].https://www.biorxiv.org/content/10.1101/164848.点此复制
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