1. Background

The aim of this study is to perform a meta-analysis of GWAS results on the date of achievement of independent locomotion during infancy. Understanding the processes underlying the timing and achievement of developmental motor milestones is critical, since they are considered to be important indicators of the child's neurological, psychomotor, and socio-emotional integrity and subsequent development. Finnish and UK longitudinal cohort studies have highlighted the importance of infant motor development by demonstrating that failure to achieve this developmental milestone at the expected age is a strong predictor of neuropsychiatric conditions, reduced physical performance and fitness over the lifecourse1,2,3,4,5,6.

Due to the relatively brief exposure of the infant to environmental influences (compared to later periods of life) most studies focusing on early developmental milestones have estimated high heritabilities. For example, although motor development throughout childhood and adolescence is expected to be a process that develops through interactions of the individual with the environment7, twin studies on infants have estimated that over 90% of the variation in motor milestone achievement is influenced by genetic factors8. This was also recently highlighted through the first GWAS study on an aspect of infant development, tooth development, a study which demonstrated the potential to identify a large number of genetic variants through GWAS meta-analysis of relatively small sample sizes9.

The study will focus on the complete, normal, distribution of the date of achievement of independent locomotion (analysis I), but also examine the delayed achievement of independent locomotion (analysis II). This is because there is support for a larger genetic contribution to delayed as compared to non-delayed development, as heritability estimates, e.g. for early language development, increase from 21% to 48% when shifting the focus from normal to delayed development10.

2. Traits of interest

For analysis I: Walking without support/unaided (age in months)

For analysis II: Walking without support unaided at 18 months (can walk - yes/no)

3. Participating studies and sample numbers

Table 1. Individuals with GWAS and phenotype data (as of 11-07-2010)

Study

Analysis I

Analysis II

NFBC1966

4000

4000

RAINE

1500

1500

MoBa

630

630

NCDS1958

-

4500

ALSPAC

-

3000

Generation R

-

2650

Tweeligenregister

?

?

Total projected sample

6130

16280

https://spreadsheets.google.com/ccc?key=0AgoCkeBwIrX4dDVjWFYtR1NQM1pfUVBrQXAyYlBBZEE&hl=nl#gid=8

2. Phenotypes / variables necessary from ALSPAC dataset

i) At 18 months: F4(d) -greater than child ' can walk alone for at least 5 steps' (Motor milestones,Denver)

ii) For exclusion:

- intellectual disability (which infants are intellectually disabled) (if availlable)

- cerebral palsy (which infants suffered from cerebral palsy) (if availlable)

iii) gestational age (covariate to be adjusted)