Unraveling the genetics of gulf war illness in diverse participants enrolled in the million veteran program
Gita A Pathak, Dora Koller, Brenda Cabrera-Mendoza, Alice B S Nono Djotsa, Frank R Wendt, Antonella De Lillo, Eleni Friligkou, Jun He, Manuela R Kouakou, Linh M Duong, Jacqueline Vahey, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, J Michael Gaziano, John Concato, Hongyu Zhao, Krishnan Radhakrishnan, Joel Gelernter, Elizabeth Gifford, Mihaela Aslan, Drew A Helmer, Elizabeth R Hauser, Renato Polimanti
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Abstract
Gulf War Illness (GWI) is a multi-symptom chronic condition that affects Veterans who served in the 1990–1991 Gulf War (GW). To generate novel information about GWI pathogenesis, we used genome-wide data available from 33 523 Veterans of diverse ancestral backgrounds who served during the 1990–1991 Gulf War era (34% deployed).
Polygenic score (PGS) analysis showed GWI pleiotropy for several traits with the strongest evidence for type-2 diabetes (T2D), anxiety, and depression. While T2D PGS was associated with higher GWI odds in GW Veterans, anxiety and depression PGSs were associated with higher odds of GWI in non-deployed GW-era Veterans.
Seven independent variants were identified (P < 5 × 10-8). Two of them were supported by independent transcriptomic and phenome-wide analyses. Rs4675853 was associated with AGXT, MAB21L4, and ATG4B transcriptomic regulation and with sex hormone-binding globulin levels. Rs138168412 was associated with AOPEP transcriptomic regulation and with respiratory function and physical strength. The TWAS identified five additional loci such as CEMIP in the cerebellum and SNCG in the adrenal gland.
The results provide a comprehensive assessment of the polygenic architecture of GWI research definitions, identifying mechanisms potentially relevant to the disease pathogenesis.
Link (Human Molecular Genetics) [Paywall]
Gita A Pathak, Dora Koller, Brenda Cabrera-Mendoza, Alice B S Nono Djotsa, Frank R Wendt, Antonella De Lillo, Eleni Friligkou, Jun He, Manuela R Kouakou, Linh M Duong, Jacqueline Vahey, Lea Steele, Rachel Quaden, Kelly M Harrington, Sarah T Ahmed, J Michael Gaziano, John Concato, Hongyu Zhao, Krishnan Radhakrishnan, Joel Gelernter, Elizabeth Gifford, Mihaela Aslan, Drew A Helmer, Elizabeth R Hauser, Renato Polimanti
[Line breaks added]
Abstract
Gulf War Illness (GWI) is a multi-symptom chronic condition that affects Veterans who served in the 1990–1991 Gulf War (GW). To generate novel information about GWI pathogenesis, we used genome-wide data available from 33 523 Veterans of diverse ancestral backgrounds who served during the 1990–1991 Gulf War era (34% deployed).
Polygenic score (PGS) analysis showed GWI pleiotropy for several traits with the strongest evidence for type-2 diabetes (T2D), anxiety, and depression. While T2D PGS was associated with higher GWI odds in GW Veterans, anxiety and depression PGSs were associated with higher odds of GWI in non-deployed GW-era Veterans.
Seven independent variants were identified (P < 5 × 10-8). Two of them were supported by independent transcriptomic and phenome-wide analyses. Rs4675853 was associated with AGXT, MAB21L4, and ATG4B transcriptomic regulation and with sex hormone-binding globulin levels. Rs138168412 was associated with AOPEP transcriptomic regulation and with respiratory function and physical strength. The TWAS identified five additional loci such as CEMIP in the cerebellum and SNCG in the adrenal gland.
The results provide a comprehensive assessment of the polygenic architecture of GWI research definitions, identifying mechanisms potentially relevant to the disease pathogenesis.
Link (Human Molecular Genetics) [Paywall]
