Selection for height genes?

Three papers on genome wide association studies & height. Identification of ten loci associated with height highlights new biological pathways in human growth, Genome-wide association analysis identifies 20 loci that influence adult height and Many sequence variants affecting diversity of adult human height. Dan MacArthur hits the major point:

ScienceDaily puts a positive spin on the story (“Scientists are beginning to develop a clearer picture of what makes some people stand head and shoulders above the rest“), but the real story is this: despite the massive scale of these studies, they’re still only capturing less than 5% of the total variance in a trait that is almost entirely (90%) genetic. This is a powerful demonstration of the inability of current GWAS technology to access the genetic variants responsible for the vast majority of heritable variation in at least some complex traits, for reasons I have previously discussed in detail.

I was wondering if there was any recent selection in the genomic regions pinpointed in the three papers, so I turned to Haplotter. Below the fold are the results….

I set Haplotter so that it looked around a 1 MB window fixed on the gene I queried. X = a hit within that window, while XX = a hit on that specific gene. The columns are pretty self-explanatory, but do note some of these genes are very close to each other. Also, I had to use aliases, and I can’t guarantee that a gene isn’t listed twice because of the usage of aliases. All in all, note much selection, huh? I wasn’t expecting much, but nice to confirm expectations….

. Gene Northern European West African East Asian Note . ACAN – – – Alias: CSPG1 . ADAMTS17 – – – . ADAMTSL3 – – – . ANAPC13 – – – . ANKFN1 – – – Alias: FLJ38335 . ANKS1 X – – . ATAD5 – – – Alias: FLJ12735 . ATXN3 – – – . BCAS3 – – – Fst – No diff. Euro-Asian in some regions . BMP2 – – – . BMP6 – – – . C18orf45 – – – . C1orf19 – – – . C20orf30 – – – . C6orf106 XX – – . CABLES1 – – – . CDK6 – – – . CENTA2 – – – Fst – No diff. Euro-Asian in some regions . CEP63 – – –

. CHCHD7 – – – . COIL – – – . CPSF2 – – – . CRLF3 – – – Fst – No diff. Euro-Asian in some regions . DCC – – – . DEF6 – – – Alias: DEFA6 . DGKE – – – . DLEU7 – – – . DNM3 – – – . DOT1L – – – . DYM – – – . E4F1 – – – Lots of stuff just below p-value in region . EFEMP1 – – – . ERVWE1 – – – Problem with haplotter . FBLN5 – – – . FUBP3 – – – . GATAD1 – – – . GDF5 X X XX Massive selection in this genomic region in Euro & Asian . GLT25D2 – – – p-value close in Asian . GNA12 – – –

. GPR126 – – – . GRB10 – – – . HHIP – – – . HIST1H1D – – – Alias: H1F3, lots of close p-values . HMGA1 X – – Signal from other gene on list . HMGA2 – – . IHH – – – p-value close in Euro . LBH – – – . LCORL – – – Alias: FLJ30696 . LIN28B – – – p-values close for Euro . LOC387103 – – – Alias: CUG2, haplotter . LYAR – – – . LYN – – – Asians fixed, so haplotter can’t detect . MOS – – – Alias: MSV . MTMR11 – – – Looks like lots of fixed stuff around…. . NACA2 – – – . NCAPG – – – Alias: CAPG . NKX2-1 – – – . NOG – – – . PAPPA – – –

. PENK – – – Asians look fixed . PEX1 – – – . PLAG1 – – – . PNPT1 – – – . PRKG2 XX – – X as well . PTCH1 – – – Haplotter error . PXMP3 – – – . RAB40C – – – . RBBP8 – – – Africans look fixed . RDHE2 – – – . RISK – – – Can’t find this gene? . RNF135 – – – p-value close for African, looks near fixed . RPS20 – – – Fixed in Asians? . SCMH1 – – – Fixed in Africans? . SCUBE3 X – – . SF3B4 – – – . SH3GL3 – – – . SOCS2 – – – . SPAG17 – – – Haplotter error . SV2A – – – Asians look fixed?

. TBX2 – – – . TBX4 – – – . TCP11 X – – Overlap with SCUBE3 . TGS1 – – – . TMED3 – – – . TRIM25 – – – . TRIP11 – – – . UQCC X X XX Lots of selection in region! Alias: BFZB . WDR60 – – – . ZBTB38 – – – . ZF HX4 – – – . ZNF462 – – – . ZNF678 – – – . ZNF76 X – – Region overlaps with others, SCUBE3