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Genetic overlap between birthweight and adult cardiometabolic diseases has implications for genomic medicine

Tekola-Ayele, Fasil ; Lee, Anthony ; Workalemahu, Tsegaselassie ; Zhang, Wei ; Shrestha, Deepika ; Amare, Azmeraw T ; Ouidir, Marion

Scientific reports, 2019-03, Vol.9 (1), p.4076-4076, Article 4076 [Periódico revisado por pares]

England: Nature Publishing Group

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Genetic overlap between birthweight and adult cardiometabolic diseases has implications for genomic medicine
Autor: Tekola-Ayele, Fasil ; Lee, Anthony ; Workalemahu, Tsegaselassie ; Zhang, Wei ; Shrestha, Deepika ; Amare, Azmeraw T ; Ouidir, Marion
Assuntos: Adult ; Adults ; Birth weight ; Birth Weight - genetics ; Cardiovascular disease ; Coronary artery ; Coronary Artery Disease - genetics ; Coronary Artery Disease - physiopathology ; Female ; Gene loci ; Genetic Loci ; Genetic Pleiotropy - genetics ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Heart diseases ; Humans ; Male ; Phenotype ; Pleiotropy ; Polymorphism, Single Nucleotide - genetics ; Therapeutic applications
É parte de: Scientific reports, 2019-03, Vol.9 (1), p.4076-4076, Article 4076
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Before implementing therapeutic genomic interventions for optimizing health in early life, comprehensive understanding of their effect on several traits across the life course is warranted. Abnorml birthweight is associated with cardiometabolic disease risk in adulthood; however, the extent of genetic pleiotropy in the association has not been comprehensively investigated. We tested for pleiotropy and enrichment of functional loci between birthweight and 15 cardiometabolic disease traits (CMD). We found significantly abundant genetic pleiotropy (P < 3.3 × 10 ) and enrichment of functional annotations (P < 3.3 × 10 ) in loci influencing both birthweight and CMD. We did not observe consistent effect directions of pleiotropic loci on the traits. A total of 67 genetic loci, of which 65 loci have been reported in previous genome-wide association studies, were associated with both birthweight and CMD at a false discovery rate of 5%. Two novel loci were associated with birthweight and adult coronary artery disease (rs2870463 in CTRB1) and with birthweight and adult waist circumference (rs12704673 in CALCR). Both loci are known to have regulatory effects on expression of nearby genes. In all, our findings revealed pervasive genetic pleiotropy in early growth and adulthood cardiometabolic diseases, implying the need for caution when considering genetic loci as therapeutic targets.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Genetic overlap between birthweight and adult cardiometabolic diseases has implications for genomic medicine

Tekola-Ayele, Fasil ; Lee, Anthony ; Workalemahu, Tsegaselassie ; Zhang, Wei ; Shrestha, Deepika ; Amare, Azmeraw T ; Ouidir, Marion

England: Nature Publishing Group

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