title: General intelligence is associated with subclinical inflammation in Nepalese children: A population-based plasma proteomics study.
abstract: Improving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to explore and quantify associations between functional plasma protein biomarkers and childhood intellectual test performance. We applied proteomics to quantify proteins in plasma samples of 249 rural Nepalese children, 6-8years of age who, 1year later at 7-9years of age, were administered the Universal Nonverbal Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were associated with UNIT scores, passing a false discovery rate threshold of 5.0% (q<0.05). UNIT scores were higher by 2.3-9.2 points for every 50% increase in relative abundance of two insulin-like growth factor binding proteins (IGFBPs), six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0-15.3 points for each 50% increase in relative abundance of 13 proteins predominantly involved in inflammation. Among them, IGFBP-acid labile subunit, orosomucoid 1 (ORM1), Apo C-I, and pyruvate kinase isoenzymes M1/M2 jointly explained 37% of the variance in UNIT scores. After additional adjustment for height-for-age Z-score and household socio-economic status as indicators of long-term nutritional and social stress, associations with 6 proteins involved in inflammation, including ORM1, α-1-antichymotrypsin, reticulocalbin 1, and 3 components of the complement cascade, remained significant (q<0.05). Using untargeted proteomics, stable, constitutive facets of subclinical inflammation were associated with lower developmental test performance in this rural South Asian child population. Plasma proteomics may offer opportunities to identify functional, antecedent biomarkers of child cognitive development.
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: slee278@jhu.edu.
authors.forename: Sun Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: kwest1@jhu.edu.
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
authors.affiliation: Mass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins School of Medicine, 733 N. Broadway Street, Baltimore, MD 21205, USA. Electronic address: rcole@jhmi.edu.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cole
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: kschulz1@jhu.edu.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: lwu2@jhu.edu.
authors.forename: Lee Shu-Fune
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: jyager1@jhu.edu.
authors.forename: James D
authors.initials: JD
authors.lastname: Yager
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: jgroopm1@jhu.edu.
authors.forename: John
authors.initials: J
authors.lastname: Groopman
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, USA. Electronic address: pchrist1@jhu.edu.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
mesh_terms: D001769:Blood / Q000378:metabolism*; D002648:Child; D002664:Child Nutritional Physiological Phenomena / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000453:epidemiology; D007360:Intelligence / Q000502:physiology*; D008297:Male; D009390:Nepal / Q000453:epidemiology; D009752:Nutritional Status / Q000502:physiology*; D040901:Proteomics
keywords: Children; Cohort study; Inflammation; Intelligence; Mass spectrometry; Nepal; Plasma proteomics; Universal Nonverbal Intelligence Test