Abstract：
:Although recent studies provide evidence for a common genetic basis between complex traits and Mendelian disorders, a thorough quantification of their overlap in a phenotype-specific manner remains elusive. Here, we have quantified the overlap of genes identified through large-scale genome-wide association studies (GWASs) for 62 complex traits and diseases with genes containing mutations known to cause 20 broad categories of Mendelian disorders. We identified a significant enrichment of genes linked to phenotypically matched Mendelian disorders in GWAS gene sets; of the total 1,240 comparisons, a higher proportion of phenotypically matched or related pairs (n = 50 of 92 [54%]) than phenotypically unmatched pairs (n = 27 of 1,148 [2%]) demonstrated significant overlap, confirming a phenotype-specific enrichment pattern. Further, we observed elevated GWAS effect sizes near genes linked to phenotypically matched Mendelian disorders. Finally, we report examples of GWAS variants localized at the transcription start site or physically interacting with the promoters of genes linked to phenotypically matched Mendelian disorders. Our results are consistent with the hypothesis that genes that are disrupted in Mendelian disorders are dysregulated by non-coding variants in complex traits and demonstrate how leveraging findings from related Mendelian disorders and functional genomic datasets can prioritize genes that are putatively dysregulated by local and distal non-coding GWAS variants.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Freund MK,Burch KS,Shi H,Mancuso N,Kichaev G,Garske KM,Pan DZ,Miao Z,Mohlke KL,Laakso M,Pajukanta P,Pasaniuc B,Arboleda VAdoi
10.1016/j.ajhg.2018.08.017subject
Has Abstractpub_date
2018-10-04 00:00:00pages
535-552issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(18)30285-4journal_volume
103pub_type
杂志文章abstract：:The reported linkage between cutaneous melanoma and the dysplastic nevus syndrome (CM/DNS) to markers located on the distal portion of the short arm of chromosome 1 was examined in three Utah kindreds ascertained for multiple cases of melanoma. Family members in these kindreds were genotyped for the two markers report...
journal_title：American journal of human genetics
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abstract：:Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of...
journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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doi：10.1086/505885
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journal_title：American journal of human genetics
pub_type： 杂志文章
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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更新日期：1982-05-01 00:00:00
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journal_title：American journal of human genetics
pub_type： 杂志文章
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journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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journal_title：American journal of human genetics
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更新日期：1996-04-01 00:00:00
