{"entity": "researcher", "timestamp": "2026-08-26T06:11:54.648Z", "family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "affiliations": ["1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA. [3] Center for Basic and Translational Obesity Research, Children's Hospital, Boston, Massachusetts, USA. [4] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [5] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/45dd48f2bc61400db209bc5543f86e0b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/45dd48f2bc61400db209bc5543f86e0b"}}, "publications": [{"entity": "publication", "iuid": "bee5ac73046042688e3e3c43444545e4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bee5ac73046042688e3e3c43444545e4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bee5ac73046042688e3e3c43444545e4"}}, "title": "Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.", "authors": [{"family": "Yang", "given": "Jian", "initials": "J", "orcid": "0000-0003-2001-2474", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/86905621292e4ef38d32bc2f0dc09525.json"}}, {"family": "Bakshi", "given": "Andrew", "initials": "A"}, {"family": "Zhu", "given": "Zhihong", "initials": "Z"}, {"family": "Hemani", "given": "Gibran", "initials": "G"}, {"family": "Vinkhuyzen", "given": "Anna A E", "initials": "AA"}, {"family": "Lee", "given": "Sang Hong", "initials": "SH"}, {"family": "Robinson", "given": "Matthew R", "initials": "MR"}, {"family": "Perry", "given": "John R B", "initials": "JR"}, {"family": "Nolte", "given": "Ilja M", "initials": "IM"}, {"family": "van Vliet-Ostaptchouk", "given": "Jana V", "initials": "JV"}, {"family": "Snieder", "given": "Harold", "initials": "H"}, {"family": "LifeLines Cohort Study", "given": "", "initials": ""}, {"family": "Esko", "given": "Tonu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45dd48f2bc61400db209bc5543f86e0b.json"}}, {"family": "Milani", "given": "Lili", "initials": "L"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Metspalu", "given": "Andres", "initials": "A"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Soranzo", "given": "Nicole", "initials": "N", "orcid": "0000-0003-1095-3852", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/751b4656807c42f9a668ebb98e8da987.json"}}, {"family": "Keller", "given": "Matthew C", "initials": "MC"}, {"family": "Wray", "given": "Naomi R", "initials": "NR", "orcid": "0000-0001-7421-3357", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58962e389d9645f694e1a9e23d820acd.json"}}, {"family": "Goddard", "given": "Michael E", "initials": "ME"}, {"family": "Visscher", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-2143-8760", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f9232be0ea244fb7ab43593e04265c2e.json"}}], "type": "journal article", "published": "2015-10-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "volume": "47", "issue": "10", "pages": "1114-1120", "issn-l": "1061-4036"}, "abstract": "We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that \u223c97% and \u223c68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all \u223c17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices.", "doi": "10.1038/ng.3390", "pmid": "26323059", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS712807"}, {"db": "pmc", "key": "PMC4589513"}, {"db": "pii", "key": "ng.3390"}, {"db": "dbGaP", "key": "PHS000090"}, {"db": "dbGaP", "key": "PHS000091"}, {"db": "dbGaP", "key": "PHS000428"}], "notes": [], "created": "2018-12-05T08:35:02.967Z", "modified": "2026-08-21T11:45:42.717Z"}, {"entity": "publication", "iuid": "673d98956940497da603abfbf4113d4b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/673d98956940497da603abfbf4113d4b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/673d98956940497da603abfbf4113d4b"}}, "title": "The impact of low-frequency and rare variants on lipid levels.", "authors": [{"family": "Surakka", "given": "Ida", "initials": "I"}, {"family": "Horikoshi", "given": "Momoko", "initials": "M"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Sarin", "given": "Antti-Pekka", "initials": "AP"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Lagou", "given": "Vasiliki", "initials": "V"}, {"family": "Marullo", "given": "Letizia", "initials": "L"}, {"family": "Ferreira", "given": "Teresa", "initials": "T"}, {"family": "Miraglio", "given": "Benjamin", "initials": "B"}, {"family": "Timonen", "given": "Sanna", "initials": "S"}, {"family": "Kettunen", "given": "Johannes", "initials": "J"}, {"family": "Pirinen", "given": "Matti", "initials": "M"}, {"family": "Karjalainen", "given": "Juha", "initials": "J"}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Isaacs", "given": "Aaron", "initials": "A"}, {"family": "Ladenvall", "given": "Claes", "initials": "C"}, {"family": "Beekman", "given": "Marian", "initials": "M"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/45dd48f2bc61400db209bc5543f86e0b.json"}}, {"family": "Ried", "given": "Janina S", "initials": "JS"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Willenborg", "given": "Christina", "initials": "C"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5894-0351", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fedf8897d75744f5b17f7c91c892acbf.json"}}, {"family": "Westra", "given": "Harm-Jan", "initials": "HJ"}, {"family": "Blades", "given": "Matthew", "initials": "M"}, {"family": "de Craen", "given": "Anton J M", "initials": "AJ"}, {"family": "de Geus", "given": "Eco J", "initials": "EJ", "orcid": "0000-0001-6022-2666", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cfe61063c4644006a01e837b72ae3345.json"}}, {"family": "Deelen", "given": "Joris", "initials": "J"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Havulinna", "given": "Aki S", "initials": "AS"}, {"family": "Hengstenberg", "given": "Christian", "initials": "C"}, {"family": "Houwing-Duistermaat", "given": "Jeanine J", "initials": "JJ"}, {"family": "Hypp\u00f6nen", "given": "Elina", "initials": "E"}, {"family": "Karssen", "given": "Lennart C", "initials": "LC", "orcid": "0000-0002-1959-342X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6fe3ae2526141e6b1bb72a9d4aca5c2.json"}}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Lyssenko", "given": "Valeriya", "initials": "V"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PK"}, {"family": "Mihailov", "given": "Evelin", "initials": "E"}, {"family": "M\u00fcller-Nurasyid", "given": "Martina", "initials": "M"}, {"family": "Mpindi", "given": "John-Patrick", "initials": "JP"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Penninx", "given": "Brenda W J H", "initials": "BW"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Pers", "given": "Tune H", "initials": "TH"}, {"family": "Peters", "given": "Annette", "initials": "A"}, {"family": "Rung", "given": "Johan", "initials": "J"}, {"family": "Smit", "given": "Johannes H", "initials": "JH"}, {"family": "Steinthorsdottir", "given": "Valgerdur", "initials": "V"}, {"family": "Tobin", "given": "Martin D", "initials": "MD"}, {"family": "Tsernikova", "given": "Natalia", "initials": "N"}, {"family": "van Leeuwen", "given": "Elisabeth M", "initials": "EM"}, {"family": "Viikari", "given": "Jorma S", "initials": "JS"}, {"family": "Willems", "given": "Sara M", "initials": "SM"}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "Schunkert", "given": "Heribert", "initials": "H"}, {"family": "Erdmann", "given": "Jeanette", "initials": "J"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J", "orcid": "0000-0002-3716-2455", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f7e6f19a0a7b4d5ba54d250fdecaee46.json"}}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Metspalu", "given": "Andres", "initials": "A"}, {"family": "Slagboom", "given": "P Eline", "initials": "PE"}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Eriksson", "given": "Johan G", "initials": "JG"}, {"family": "Jula", "given": "Antti", "initials": "A"}, {"family": "Salomaa", "given": "Veikko", "initials": "V"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Power", "given": "Christine", "initials": "C"}, {"family": "Raitakari", "given": "Olli T", "initials": "OT"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "J\u00e4rvelin", "given": "Marjo-Riitta", "initials": "MR"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Franke", "given": "Lude", "initials": "L", "orcid": "0000-0002-5159-8802", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e0a825c1d31c458e872fa6c79d30f02e.json"}}, {"family": "Ikonen", "given": "Elina", "initials": "E"}, {"family": "Kallioniemi", "given": "Olli", "initials": "O", "orcid": "0000-0002-3231-0332", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/cb8605b07c884323afe4e1f2da37a031.json"}}, {"family": "Pieti\u00e4inen", "given": "Vilja", "initials": "V"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Palotie", "given": "Aarno", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Prokopenko", "given": "Inga", "initials": "I"}, {"family": "Ripatti", "given": "Samuli", "initials": "S"}, {"family": "ENGAGE Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2015-06-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "volume": "47", "issue": "6", "pages": "589-597", "issn-l": "1061-4036"}, "abstract": "Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.", "doi": "10.1038/ng.3300", "pmid": "25961943", "labels": [], "xrefs": [{"db": "mid", "key": "EMS67068"}, {"db": "pmc", "key": "PMC4757735"}, {"db": "pii", "key": "ng.3300"}], "notes": [], "created": "2018-12-05T08:43:57.674Z", "modified": "2026-08-21T11:45:40.489Z"}]}