Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight

doi:10.1111/dmcn.14383

Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight

Pediatrics

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Abstract

Aim: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW). Method: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0–14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP. Results: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates. Interpretation: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP. What this paper adds: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy.

Original language	English
Pages (from-to)	750-757
Number of pages	8
Journal	Developmental Medicine and Child Neurology
Volume	62
Issue number	6
DOIs	https://doi.org/10.1111/dmcn.14383
State	Published - Jun 1 2020

Bibliographical note

Funding Information:
Joshua L Levy and Scott A McDonald (both Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC, USA) are additional authors of the paper. The members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network are as follows: C Michael Cotton (Department of Pediatrics, Duke University, Durham, NC); Grier Page (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Waldemar A Carlo (Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL); Edward F Bell (University of Iowa, Department of Pediatrics, Iowa City, IA); Ronald N Goldberg (Department of Pediatrics, Duke University, Durham, NC); Kurt Schibler (Department of Pediatrics, University of Cincinnati, Cincinnati, OH); Rosemary D Higgins (Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD); Beena G Sood (Department of Pediatrics, Wayne State University, Detroit, MI); David K Stevenson (Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA); Barbara J Stoll (Emory University School of Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA); Krisa P Van Meurs (Department of Pediatrics, Wayne State University, Detroit, MI); Karen J Johnson (University of Iowa, Department of Pediatrics, Iowa City, IA); Abhik Das (Social, Statistical and Environmental Sciences, RTI International, Rockville, MD); Scott A McDonald (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Kristin M Zaterka-Baxter (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Jeffrey C Murray (University of Iowa, Department of Pediatrics, Iowa City, IA). Grant and other information can be found in Appendix S1 (online supporting information).

Publisher Copyright:
© 2019 Mac Keith Press

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Developmental Neuroscience
Clinical Neurology

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10.1111/dmcn.14383

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@article{33785368278343b0845b662f4f5d2b68,

title = "Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight",

abstract = "Aim: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW). Method: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0–14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP. Results: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates. Interpretation: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP. What this paper adds: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy.",

author = "Gordon Worley and Erickson, {Stephen W.} and Gustafson, {Kathryn E.} and Nikolova, {Yuliya S.} and Ashley-Koch, {Allison E.} and Belsky, {Daniel W.} and Goldstein, {Ricki F.} and Page, {Grier P.} and Cotten, {C. Michael} and Carlo, {Waldemar A.} and Bell, {Edward F.} and Goldberg, {Ronald N.} and Kurt Schibler and Higgins, {Rosemary D.} and Sood, {Beena G.} and Stevenson, {David K.} and Stoll, {Barbara J.} and {Van Meurs}, {Krisa P.} and Johnson, {Karen J.} and Abhik Das and McDonald, {Scott A.} and Zaterka-Baxter, {Kristin M.} and Murray, {Jeffrey C.}",

note = "Funding Information: Joshua L Levy and Scott A McDonald (both Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC, USA) are additional authors of the paper. The members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network are as follows: C Michael Cotton (Department of Pediatrics, Duke University, Durham, NC); Grier Page (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Waldemar A Carlo (Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL); Edward F Bell (University of Iowa, Department of Pediatrics, Iowa City, IA); Ronald N Goldberg (Department of Pediatrics, Duke University, Durham, NC); Kurt Schibler (Department of Pediatrics, University of Cincinnati, Cincinnati, OH); Rosemary D Higgins (Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD); Beena G Sood (Department of Pediatrics, Wayne State University, Detroit, MI); David K Stevenson (Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA); Barbara J Stoll (Emory University School of Medicine, Department of Pediatrics, Children{\textquoteright}s Healthcare of Atlanta, Atlanta, GA); Krisa P Van Meurs (Department of Pediatrics, Wayne State University, Detroit, MI); Karen J Johnson (University of Iowa, Department of Pediatrics, Iowa City, IA); Abhik Das (Social, Statistical and Environmental Sciences, RTI International, Rockville, MD); Scott A McDonald (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Kristin M Zaterka-Baxter (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Jeffrey C Murray (University of Iowa, Department of Pediatrics, Iowa City, IA). Grant and other information can be found in Appendix S1 (online supporting information). Publisher Copyright: {\textcopyright} 2019 Mac Keith Press",

year = "2020",

month = jun,

day = "1",

doi = "10.1111/dmcn.14383",

language = "English",

volume = "62",

pages = "750--757",

number = "6",

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TY - JOUR

T1 - Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight

AU - Worley, Gordon

AU - Erickson, Stephen W.

AU - Gustafson, Kathryn E.

AU - Nikolova, Yuliya S.

AU - Ashley-Koch, Allison E.

AU - Belsky, Daniel W.

AU - Goldstein, Ricki F.

AU - Page, Grier P.

AU - Cotten, C. Michael

AU - Carlo, Waldemar A.

AU - Bell, Edward F.

AU - Goldberg, Ronald N.

AU - Schibler, Kurt

AU - Higgins, Rosemary D.

AU - Sood, Beena G.

AU - Stevenson, David K.

AU - Stoll, Barbara J.

AU - Van Meurs, Krisa P.

AU - Johnson, Karen J.

AU - Das, Abhik

AU - McDonald, Scott A.

AU - Zaterka-Baxter, Kristin M.

AU - Murray, Jeffrey C.

N1 - Funding Information: Joshua L Levy and Scott A McDonald (both Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC, USA) are additional authors of the paper. The members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network are as follows: C Michael Cotton (Department of Pediatrics, Duke University, Durham, NC); Grier Page (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Waldemar A Carlo (Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL); Edward F Bell (University of Iowa, Department of Pediatrics, Iowa City, IA); Ronald N Goldberg (Department of Pediatrics, Duke University, Durham, NC); Kurt Schibler (Department of Pediatrics, University of Cincinnati, Cincinnati, OH); Rosemary D Higgins (Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD); Beena G Sood (Department of Pediatrics, Wayne State University, Detroit, MI); David K Stevenson (Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA); Barbara J Stoll (Emory University School of Medicine, Department of Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA); Krisa P Van Meurs (Department of Pediatrics, Wayne State University, Detroit, MI); Karen J Johnson (University of Iowa, Department of Pediatrics, Iowa City, IA); Abhik Das (Social, Statistical and Environmental Sciences, RTI International, Rockville, MD); Scott A McDonald (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Kristin M Zaterka-Baxter (Social, Statistical and Environmental Sciences, RTI International, Research Triangle Park, NC); Jeffrey C Murray (University of Iowa, Department of Pediatrics, Iowa City, IA). Grant and other information can be found in Appendix S1 (online supporting information). Publisher Copyright: © 2019 Mac Keith Press

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Aim: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW). Method: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0–14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP. Results: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates. Interpretation: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP. What this paper adds: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy.

AB - Aim: To determine if genetic variation associated with decreased dopamine neurotransmission predicts a decrease in motor development in a convenience cohort study of infants born extremely-low-birthweight (ELBW). Method: Four hundred and ninety-eight infants born ELBW had genome-wide genotyping and a neurodevelopmental evaluation at 18 to 22 months of age, corrected for preterm birth. A polygenic risk score (PRS) was created to combine into one predictor variable the hypothesized influences on motor development of alleles at seven independent single nucleotide polymorphisms previously associated with relative decreases in both dopamine neurotransmission and motor learning, by summing the number of alleles present in each infant (range=0–14). The motor development outcome was the Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development, Second Edition. The linear regression models were adjusted for seven clinical and four genetic ancestry covariates. The mean PRS of infants with cerebral palsy (CP) was compared to those without CP. Results: PRS was inversely related to PDI (p=0.011). Each 1-point increase in PRS resulted in an average decrease in PDI of 1.37 points. Patients with CP did not have a greater mean PRS than those without (p=0.67), both with and without adjustment for covariates. Interpretation: Genetic variation that favors a decrease in dopamine neurotransmission predisposes to a decrease in motor development in infants born ELBW, but not to the diagnosis of CP. What this paper adds: Genetic variation in dopamine neurotransmission was associated with a decrease in motor development in infants born at an extremely-low-birthweight. It does not predispose to the diagnosis of cerebral palsy.

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Genetic variation in dopamine neurotransmission and motor development of infants born extremely-low-birthweight

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