Rs143383

[PMID 17384641] rs143383 showed significant association with hip osteoarthritis in two independent Japanese populations. It also showed association with knee osteoarthritis in Japanese and Chinese populations.

[PMID 17676627] is *not* a risk factor for osteoarthritis in Greek Caucasians

A subsequent study showed that the same risk allele, rs143383(T), was (somewhat) associated with osteoarthritis in European populations. The odds ratio was 1.10 for the allele, 1.28 for carrier status (p=0.03, p=0.004, respectively). The (T) allele appears to make less GDF5 protein, which eventually renders an individual somewhat more susceptible to osteoarthritis.[PMID 17616513]

A meta-analysis combining data from 11,000+ individuals as well as both European and Asian populations found strong evidence (p < 0.0004) confirming increased risk for osteoarthritis from the rs143383(T) allele. The best model is a dominant one, and the odds ratio reported is 1.21 in general and 1.48 for the dominant model.[PMID 18299287]

Another meta-analysis of 14 studies concluded that rs143383 did indeed show significant association with osteoarthritis, at least for knee osteoarthritis, and probably for hand and hip (but to a lesser degree). The effect size wasn't large, though (odds ratio 1.15, CI: 1.09-1.22, p = 9.4 x 10e-7).[PMID 19479880]

A haplotype of rs143383 and rs6060369 can be defined, which also links osteoarthritis to height since rs6060369 was linked to height in a study ultimately involving over 28,000 individuals.[PMID 18193045]

The Medpage article on this finding notes that rs143383 was previously shown to be associated with increased risk for osteoarthritis and in this recent study [PMID 18193045] it was significantly associated with shorter height in the initial scans, at p=2.70x10e-5.

Note that the authors of [PMID 18193045] refer to rs143383 in the opposite orientation compared to it's entry in dbSNP.

[PMID 18947434] A study of 338 Han Chinese children affected by congenital dysplasia of the hip revealed that rs143383(T) alleles conferred a 1.4x increased risk for the disorder, particularly in females (odds ratio 1.43, CI: 1.11 - 1.85, p = 0.0078).

[PMID 19029166] A study of 6,365 elderly Caucasian men and women observed significant association between rs143383 and osteoarthritis, height, bone size and fracture risk in women.

[PMID 19565498] Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism

[PMID 20499385] Different risk factors are involved in clinically severe large joint osteoarthritis according to the presence of hand interphalangeal nodes

[PMID 20633687] Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population

[PMID 21128259] GDF5 SNP rs143383 is associated with lumbar disc disease in northern European women

[PMID 21542882] Knee osteoarthritis, lumbar-disc degeneration and developmental dysplasia of the hip - an emerging genetic overlap

[PMID 22284607] Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis.