Telomere length is associated with growth in children in rural Bangladesh

  1. Audrie Lin  Is a corresponding author
  2. Andrew N Mertens
  3. Benjamin F Arnold
  4. Sophia Tan
  5. Jue Lin
  6. Christine P Stewart
  7. Alan E Hubbard
  8. Shahjahan Ali
  9. Jade Benjamin-Chung
  10. Abul K Shoab
  11. Md Ziaur Rahman
  12. Syeda L Famida
  13. Md Saheen Hossen
  14. Palash Mutsuddi
  15. Salma Akther
  16. Mahbubur Rahman
  17. Leanne Unicomb
  18. Ruchira Tabassum Naved
  19. Md Mahfuz Al Mamun
  20. Kausar Parvin
  21. Firdaus S Dhabhar
  22. Patricia Kariger
  23. Lia CH Fernald
  24. Stephen P Luby
  25. John M Colford Jr
  1. Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, United States
  2. Francis I. Proctor Foundation, University of California San Francisco, United States
  3. Department of Biochemistry and Biophysics, University of California, San Francisco, United States
  4. Department of Nutrition, University of California, Davis, United States
  5. Infectious Disease Division, International Centre for Diarrhoeal Disease Research, Bangladesh
  6. Department of Epidemiology & Population Health, Stanford University, United States
  7. Health System and Population Studies Division, International Centre for Diarrhoeal Disease Research, Bangladesh
  8. Department of Psychiatry & Behavioral Sciences, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, United States
  9. Division of Community Health Sciences, School of Public Health, University of California, Berkeley, United States
  10. Division of Infectious Diseases and Geographic Medicine, Stanford University, United States
3 figures, 5 tables and 6 additional files

Figures

Diagram of participants at each phase of the telomere length and growth substudy within the WASH Benefits trial.
Figure 2 with 3 supplements
Adjusted association between telomere length and growth.

Adjusted differences in mean anthropometry Z score between 10th and 90th percentile of telomere measure. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 1
Association between telomere length at Year 1 and concurrent and subsequent growth.

Spline curves of telomere length at Year 1 and anthropometric Z scores at Years 1 and 2, change in anthropometric Z scores, and growth velocity. T/S Ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 2
Association between telomere length at Year 2 and concurrent growth.

Spline curves of telomere length at Year 2 and anthropometric Z scores at Year 2. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 2—figure supplement 3
Association between change in telomere length between Years 1 and 2 and growth.

Spline curves of change in telomere length between Years 1 and 2 and anthropometric Z scores at Year 2, change in anthropometric Z scores, and growth velocity. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 3 with 2 supplements
Regression to the mean assessment: association between telomere length at Year 1 and change in telomere length between Years 1 and 2.

T/S ratio = unit for relative telomere length.

Figure 3—figure supplement 1
Regression to the mean comparison of unadjusted association between change in telomere length and growth.

Unadjusted differences in mean anthropometry Z score between 10th and 90th percentile of change in telomere length between Years 1 and 2. Unadjusted associations corrected for the regression to the mean (RTM) effect using the equation in Verhulst et al., 2013. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

Figure 3—figure supplement 2
Regression to the mean comparison of adjusted association between change in telomere length and growth.

Adjusted differences in mean anthropometry Z score between 10th and 90th percentile of change in telomere length between Years 1 and 2. Adjusted associations corrected for the regression to the mean (RTM) effect using the equation in Verhulst et al., 2013. LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score. Adjusted for pre-specified covariates: Child age, child sex, birth order, prior child length and weight measurements from Year 1 (included in Year 2 outcomes only), season of measurement, time between anthropometry measurements (included in growth velocity and change in growth measurements between Year 1 and Year 2 outcomes only), caregiver-reported diarrhoea, mother’s age, mother’s height, mother’s education level, mother’s Center for Epidemiologic Studies Depression Scale Revised (CESD-R) score, mother’s Perceived Stress Scale score, mother’s lifetime exposure to physical, sexual, and emotional intimate partner violence, household food insecurity, number of children <18 years in the household, number of individuals living in the compound, distance in minutes to the primary water source, household floor materials, household wall materials, household electricity, and household assets (wardrobe, table, chair, clock, khat, chouki, radio, television, refrigerator, bicycle, motorcycle, sewing machine, mobile phone, cattle, goats, and chickens), and treatment arm (control or N + WSH) (Supplementary file 1a).

Tables

Table 1
Characteristics of participants.
N (%) or median (IQR)
ChildFemale (%)417 (51%)
Age (months) at Year 114.3 (12.6, 15.6)
Age (months) at Year 228.2 (26.9, 29.6)
Months between telomere length measurements at Year 1 and Year 213.9 (13.5, 14.7)
Telomere length at Year 1T/S ratio*1.42 (1.28, 1.56)
Telomere length at Year 2T/S ratio*1.43 (1.29, 1.58)
Change in telomere length between Year 1 and Year 2T/S ratio*0.04 (-0.22, 0.25)
Anthropometry (age 3 months, Month 3)Length-for-age Z score–1.28 (–1.99, –0.53)
Weight-for-age Z score–1.18 (–1.84, –0.50)
Weight-for-length Z score–0.26 (–1.11, 0.44)
Head circumference-for-age Z score–1.73 (–2.39, –1.01)
Anthropometry (age 14 months, Year 1)Length-for-age Z score–1.41 (–2.08, –0.77)
Weight-for-age Z score–1.30 (–1.98, –0.68)
Weight-for-length Z score–0.89 (–1.60, –0.25)
Head circumference-for-age Z score–1.81 (–2.40, –1.19)
Anthropometry (age 28 months, Year 2)Length-for-age Z score–1.54 (–2.25, –0.94)
Weight-for-age Z score–1.55 (–2.09, –0.90)
Weight-for-length Z score–1.00 (–1.59,–0.37)
Head circumference-for-age Z score–1.78 (–2.37, –1.22)
Diarrhoea (age 14 months, Year 1)Caregiver-reported 7 day recall (%)104 (14%)
Diarrhoea (age 28 months, Year 2)Caregiver-reported 7 day recall (%)56 (8%)
MotherAge (years)23 (20, 27)
Anthropometry at enrolmentHeight (cm)150.5 (147.1, 153.9)
EducationSchooling completed (years)7 (4, 9)
Depression at Year 1CESD-R score**10 (6, 16)
Depression at Year 2CESD-R score**10 (5, 17)
Perceived stress at Year 2Perceived Stress Scale score14 (10, 18)
Physical, sexual, or emotional intimate partner violenceAny lifetime exposure: number of women (%)398 (56%)
  1. *The unit for relative telomere length is the T/S ratio. Telomere length was measured by quantitative PCR (qPCR), a method that determines relative telomere length by measuring the factor by which each DNA sample differs from a reference DNA sample in its ratio of telomere repeat copy number (T) to single-copy gene copy number (S).

  2. **CESD-R = Center for Epidemiologic Studies Depression Scale Revised.

Table 2
Association between telomere length at Year 1 and growth.
ExposureOutcomeN10th percentile90th percentileOutcome, 90th percentile vs. 10th percentile
Adjusted
Predicted outcome at 10th percentilePredicted outcome at 90th percentileCoefficient (95% CI)p-value
Telomere length at Year 1 (T/S ratio)LAZ Year 16381.21.7–1.54–1.310.23 (0.05, 0.42)0.01*
WAZ Year 16381.21.7–1.21–1.200.01 (–0.2, 0.23)0.91
WLZ Year 16361.21.7–0.68–0.83–0.16 (-0.36, 0.05)0.14
HCZ Year 16381.21.7–1.82–1.810.01 (–0.18, 0.2)0.94
LAZ Year 25421.21.7–1.51–1.450.06 (–0.04, 0.16)0.22
WAZ Year 25651.21.7–1.77–1.700.07 (–0.03, 0.17)0.18
WLZ Year 25681.21.7–0.99–1.01–0.03 (–0.14, 0.09)0.68
HCZ Year 25651.21.7–1.85–1.810.04 (–0.18, 0.25)0.73
Change in LAZ between Year 1 and Year 25681.21.7–0.23–0.28–0.05 (–0.14, 0.04)0.29
Change in WAZ between Year 1 and Year 25721.21.7–0.37–0.380 (–0.11, 0.1)0.94
Change in WLZ between Year 1 and Year 25651.21.7–0.24–0.200.04 (–0.09, 0.17)0.56
Change in HCZ between Year 1 and Year 25451.21.7–0.16–0.110.06 (–0.05, 0.17)0.31
Length velocity between Year 1 and Year 25411.21.70.800.800 (–0.02, 0.03)0.79
Weight velocity between Year 1 and Year 25411.21.70.150.150 (–0.01, 0.01)0.74
Head circumference velocity between Year 1 and Year 25451.21.70.150.160.01 (0, 0.02)0.13
  1. N, 10th percentile, and 90th percentile are from the adjusted analyses.

  2. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

  3. *

    p-value<0.05 after adjusting for multiple comparisons using the Benjamini–Hochberg procedure.

  4. Adjusted for pre-specified covariates: Child age, child sex, birth order, prior child length, and weight measurements (included in Year 2 outcomes only), time between anthropometry measurements (included in growth velocity and change in growth measurements between Year 1 and Year 2 outcomes only), season of measurement, caregiver-reported diarrhoea, mother’s age, mother’s height, mother’s education level, mother’s Center for Epidemiologic Studies Depression Scale Revised (CESD-R) score, mother’s Perceived Stress Scale score, mother’s lifetime exposure to physical, sexual, and emotional intimate partner violence, household food insecurity, number of children < 18 years in the household, number of individuals living in the compound, distance in minutes to the primary water source, household floor materials, household wall materials, household electricity, and household assets (wardrobe, table, chair, clock, khat, chouki, radio, television, refrigerator, bicycle, motorcycle, sewing machine, mobile phone, cattle, goats, and chickens), and treatment arm (control or N + WSH) (Supplementary file 1a).

Table 3
Association between telomere length at Year 2 and growth.
ExposureOutcomeN10th percentile90th percentileOutcome, 90th percentile vs. 10th percentile
Adjusted*
Predicted outcome at 10th percentilePredicted outcome at 90th percentileCoefficient (95% CI)p-value
Telomere length at Year 2 (T/S ratio)LAZ Year 25921.11.7−1.68−1.60.08 (−0.03, 0.19)0.17
WAZ Year 26111.11.7−1.84−1.80.06 (−0.05, 0.16)0.3
WLZ Year 26151.11.7−0.98−1.1−0.08 (−0.2, 0.04)0.18
HCZ Year 26121.11.7−1.94−1.90 (−0.18, 0.17)0.98
  1. N, 10th percentile, and 90th percentile are from the adjusted analyses.

  2. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

  3. *

    Adjusted for pre-specified covariates: Child age, child sex, birth order, prior child length and weight measurements from Year 1, season of measurement, caregiver-reported diarrhoea, mother’s age, mother’s height, mother’s education level, mother’s Center for Epidemiologic Studies Depression Scale Revised (CESD-R) score, mother’s Perceived Stress Scale score, mother’s lifetime exposure to physical, sexual, and emotional intimate partner violence, household food insecurity, number of children <18 years in the household, number of individuals living in the compound, distance in minutes to the primary water source, household floor materials, household wall materials, household electricity, and household assets (wardrobe, table, chair, clock, khat, chouki, radio, television, refrigerator, bicycle, motorcycle, sewing machine, mobile phone, cattle, goats, and chickens), and treatment arm (control or N + WSH) (Supplementary file 1a).

Table 4
Association between change in telomere length and growth.
ExposureOutcomeN10th percentile90th percentileOutcome, 90th percentile vs. 10th percentile
Adjusted*
Predicted outcome at 10th percentilePredicted outcome at 90th percentileCoefficient (95% CI)p-value
Change in telomere length between Year 1 and Year 2 (T/S ratio)LAZ Year 2523−0.430.44−1.47−1.50−0.03 (−0.13, 0.07)0.62
WAZ Year 2541−0.430.44−1.72−1.76−0.03 (−0.13, 0.07)0.53
WLZ Year 2545−0.430.44−0.98−1.05−0.07 (−0.18, 0.04)0.24
HCZ Year 2543−0.430.44−1.83−1.90−0.08 (−0.24, 0.09)0.36
Change in LAZ between Year 1 and Year 2545−0.430.44−0.23−0.230 (−0.09, 0.08)1
Change in WAZ between Year 1 and Year 2547−0.430.44−0.36−0.40−0.04 (−0.13, 0.05)0.36
Change in WLZ between Year 1 and Year 2543−0.430.44−0.23−0.27−0.04 (−0.16, 0.08)0.53
Change in HCZ between Year 1 and Year 2525−0.430.44−0.14−0.19−0.05 (−0.15, 0.06)0.39
Length velocity between Year 1 and Year 2522−0.430.440.840.82−0.01 (−0.03, 0.01)0.29
Weight velocity between Year 1 and Year 2522−0.430.440.150.150 (−0.01, 0.01)0.48
Head circumference velocity between Year 1 and Year 2525−0.430.440.160.15−0.01 (−0.02, 0.01)0.35
  1. N, 10th percentile, and 90th percentile are from the adjusted analyses.

  2. T/S ratio = unit for relative telomere length; LAZ = length-for-age Z score; WAZ = weight-for-age Z score; WLZ = weight-for-length Z score; HCZ = head circumference-for-age Z score.

  3. *

    Adjusted for pre-specified covariates: Child age, child sex, birth order, prior child length and weight measurements from Year 1 (included in Year 2 outcomes only), season of measurement, time between anthropometry measurements (included in growth velocity and change in growth measurements between Year 1 and Year 2 outcomes only), caregiver-reported diarrhoea, mother’s age, mother’s height, mother’s education level, mother’s Center for Epidemiologic Studies Depression Scale Revised (CESD-R) score, mother’s Perceived Stress Scale score, mother’s lifetime exposure to physical, sexual, and emotional intimate partner violence, household food insecurity, number of children <18 years in the household, number of individuals living in the compound, distance in minutes to the primary water source, household floor materials, household wall materials, household electricity, and household assets (wardrobe, table, chair, clock, khat, chouki, radio, television, refrigerator, bicycle, motorcycle, sewing machine, mobile phone, cattle, goats, and chickens), and treatment arm (control or N + WSH) (Supplementary file 1a).

Author response table 1
Twin Sensitivity Analysis: Association Between Telomere Length at Year 1 and Growth.
ExposureOutcomeN10th Percentile90th PercentileOutcome, 90th Percentile v. 10th Percentile
Adjusted
Predicted Outcome at 10th PercentilePredicted Outcome at 90th PercentileCoefficient (95% CI)P-value
Telomere length at Year 1LAZ Year 16351.21.7-1.52-1.320.2 (0.02, 0.37)0.03*
WAZ Year 16341.21.7-1.18-1.20-0.02 (-0.22, 0.19)0.89
WLZ Year 16331.21.7-0.66-0.83-0.17 (-0.37, 0.03)0.10
HCZ Year 16351.21.7-1.72-1.73-0.01 (-0.2, 0.18)0.92
LAZ Year 25401.21.7-1.50-1.440.06 (-0.04, 0.16)0.21
WAZ Year 25401.21.7-1.74-1.690.05 (-0.05, 0.16)0.35
WLZ Year 25661.21.7-0.97-1.00-0.03 (-0.15, 0.08)0.58
HCZ Year 25631.21.7-1.87-1.820.04 (-0.13, 0.21)0.65
Change in LAZ between Year 1 and Year 25661.21.7-0.24-0.29-0.05 (-0.14, 0.05)0.35
Change in WAZ between Year 1 and Year 25701.21.7-0.37-0.38-0.01 (-0.11, 0.09)0.87
Change in WLZ between Year 1 and Year 25631.21.7-0.25-0.220.03 (-0.1, 0.17)0.66
Change in HCZ between Year 1 and Year 25431.21.7-0.16-0.110.06 (-0.05, 0.17)0.32
Length velocity between Year 1 and Year 25391.21.70.800.800 (-0.02, 0.03)0.76
Weight velocity between Year 1 and Year 25391.21.70.150.150 (-0.01, 0.01)0.84
Head circumference velocity between Year 1 and Year 25431.21.70.150.160.01 (0, 0.02)0.14
  1. N, 10th Percentile, and 90th Percentile are from the adjusted analyses.

  2. P-value < 0.05 after adjusting for multiple comparisons using the Benjamini-Hochberg procedure.

Additional files

Supplementary file 1

Supplementary tables.

(a) Pre-specified covariates screened for inclusion in fully adjusted models. (b) Association Between Telomere Length at Year 1 and Growth. (c) Association Between Telomere Length at Year 2 and Growth. (d) Association Between Change in Telomere Length and Growth. (e) Post-hoc Analyses: Association Between Growth at Month 3 and Subsequent Telomere Length. (f) Post-hoc Analyses: Association Between Growth at Year 1 and Subsequent Telomere Length. (g) Post-hoc Analyses: Association Between Change in Growth and Telomere Length. (h) Post-hoc Analyses: Association Between Growth Velocity and Telomere Length.

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Source code 1

Source code for Tables 24 and Supplementary file 1b–1d.

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Source code 2

Source code for Supplementary file 1e–1h.

https://cdn.elifesciences.org/articles/60389/elife-60389-supp3-v2.zip
Source data 1

Source data for Supplementary file 1e–1h.

https://cdn.elifesciences.org/articles/60389/elife-60389-supp4-v2.zip
Source data 2

Source data for Tables 24 and Supplementary file 1b–1d.

https://cdn.elifesciences.org/articles/60389/elife-60389-supp5-v2.zip

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  1. Audrie Lin
  2. Andrew N Mertens
  3. Benjamin F Arnold
  4. Sophia Tan
  5. Jue Lin
  6. Christine P Stewart
  7. Alan E Hubbard
  8. Shahjahan Ali
  9. Jade Benjamin-Chung
  10. Abul K Shoab
  11. Md Ziaur Rahman
  12. Syeda L Famida
  13. Md Saheen Hossen
  14. Palash Mutsuddi
  15. Salma Akther
  16. Mahbubur Rahman
  17. Leanne Unicomb
  18. Ruchira Tabassum Naved
  19. Md Mahfuz Al Mamun
  20. Kausar Parvin
  21. Firdaus S Dhabhar
  22. Patricia Kariger
  23. Lia CH Fernald
  24. Stephen P Luby
  25. John M Colford Jr
(2021)
Telomere length is associated with growth in children in rural Bangladesh
eLife 10:e60389.
https://doi.org/10.7554/eLife.60389