TY - JOUR
T1 - Inferring Identical-by-Descent Sharing of Sample Ancestors Promotes High-Resolution Relative Detection
AU - Ramstetter, Monica D.
AU - Shenoy, Sushila A.
AU - Dyer, Thomas D.
AU - Lehman, Donna M.
AU - Curran, Joanne E
AU - Duggirala, Ravindranath
AU - Blangero, John C
AU - Mezey, Jason G.
AU - Williams, Amy L.
N1 - Funding Information:
We thank the anonymous reviewers for helpful suggestions and Brian and Sharon Browning for support with Refined IBD. This work was supported by a National Science Foundation Graduate Research Fellowship grant number DGE-1144153 to M.D.R.; Qatar National Research Fund grant NPRP 7-1425-3-370 to J.G.M.; an Alfred P. Sloan Research Fellowship ( FG-2015-65992 ), and a seed grant from Nancy and Peter Meinig to A.L.W. The SAMAFS are supported by NIH grants R01 HL0113323 , P01 HL045222 , R01 DK047482 , and R01 DK053889 . This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from https://www.wtccc.org.uk . Funding for the project was provided by the Wellcome Trust under awards 076113 , 085475 , and 090355 .
Funding Information:
We thank the anonymous reviewers for helpful suggestions and Brian and Sharon Browning for support with Refined IBD. This work was supported by a National Science Foundation Graduate Research Fellowship grant number DGE-1144153 to M.D.R.; Qatar National Research Fund grant NPRP 7-1425-3-370 to J.G.M.; an Alfred P. Sloan Research Fellowship (FG-2015-65992), and a seed grant from Nancy and Peter Meinig to A.L.W. The SAMAFS are supported by NIH grants R01 HL0113323, P01 HL045222, R01 DK047482, and R01 DK053889. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from https://www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under awards 076113, 085475, and 090355.
Publisher Copyright:
© 2018 American Society of Human Genetics
PY - 2018/7/5
Y1 - 2018/7/5
N2 - As genetic datasets increase in size, the fraction of samples with one or more close relatives grows rapidly, resulting in sets of mutually related individuals. We present DRUID—deep relatedness utilizing identity by descent—a method that works by inferring the identical-by-descent (IBD) sharing profile of an ungenotyped ancestor of a set of close relatives. Using this IBD profile, DRUID infers relatedness between unobserved ancestors and more distant relatives, thereby combining information from multiple samples to remove one or more generations between the deep relationships to be identified. DRUID constructs sets of close relatives by detecting full siblings and also uses an approach to identify the aunts/uncles of two or more siblings, recovering 92.2% of real aunts/uncles with zero false positives. In real and simulated data, DRUID correctly infers up to 10.5% more relatives than PADRE when using data from two sets of distantly related siblings, and 10.7%–31.3% more relatives given two sets of siblings and their aunts/uncles. DRUID frequently infers relationships either correctly or within one degree of the truth, with PADRE classifying 43.3%–58.3% of tenth degree relatives in this way compared to 79.6%–96.7% using DRUID.
AB - As genetic datasets increase in size, the fraction of samples with one or more close relatives grows rapidly, resulting in sets of mutually related individuals. We present DRUID—deep relatedness utilizing identity by descent—a method that works by inferring the identical-by-descent (IBD) sharing profile of an ungenotyped ancestor of a set of close relatives. Using this IBD profile, DRUID infers relatedness between unobserved ancestors and more distant relatives, thereby combining information from multiple samples to remove one or more generations between the deep relationships to be identified. DRUID constructs sets of close relatives by detecting full siblings and also uses an approach to identify the aunts/uncles of two or more siblings, recovering 92.2% of real aunts/uncles with zero false positives. In real and simulated data, DRUID correctly infers up to 10.5% more relatives than PADRE when using data from two sets of distantly related siblings, and 10.7%–31.3% more relatives given two sets of siblings and their aunts/uncles. DRUID frequently infers relationships either correctly or within one degree of the truth, with PADRE classifying 43.3%–58.3% of tenth degree relatives in this way compared to 79.6%–96.7% using DRUID.
KW - cryptic relatedness
KW - identical by descent
KW - pedigree reconstruction
KW - relationship inference
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U2 - 10.1016/j.ajhg.2018.05.008
DO - 10.1016/j.ajhg.2018.05.008
M3 - Article
C2 - 29937093
AN - SCOPUS:85048294695
SN - 0002-9297
VL - 103
SP - 30
EP - 44
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -