Table 1 (a) Results of a case–control association analysis conditioning on individuals with the susceptibility variant within LPHN3 (P<0.000005, Pcorrected<0.005), with 48 affected cases and 39 unaffected controls; (b) results of a TDT analysis in trios derived from nuclear families from the Paisa genetic isolate, Germany and two primarily European American samples (USA1—National Human Genome Research Institute, Bethesda, MD, USA; USA2—Children's Hospital of Philadelphia, Philadelphia, PA, USA); (c) results of the fixed-effect meta-analysis on the four samples

From: A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD

(a) a

LPHN3 b

11q haplotype c

Cases (frequency, %)

Controls (frequency, %)

OR (95% CI)

P-value

G

GG

55 (57)

18 (23)

4.47 (2.30, 8.69)

P<0.000005,

G

Else

41 (43)

60 (77)

 

Pcorrected<0.005

(b) d

Sample

LPHN3 b

11q haplotype e

Transmitted (frequency, %)

Not transmitted (frequency, %)

OR (95% CI)

P-value

Paisa

G

GG

31 (10.2)

10 (3.3)

3.14 (1.49, 6.62)

0.0027

 

G

Else

39 (12.9)

27 (8.9)

1.46 (0.85, 2.51)

0.1661

 

Else

GG

78 (25.7)

108 (35.8)

0.73 (0.51, 1.06)

0.0943

 

Else

Else

155 (51.2)

157 (52)

Reference

Reference

German

G

GG

26 (7.9)

13 (3.9)

1.91 (0.95, 3.84)

0.0706

 

G

Else

58 (17.6)

50 (15.2)

1.11 (0.72, 1.71)

0.6505

 

Else

GG

75 (22.7)

104 (31.5)

0.69 (0.48, 0.99)

0.0449

 

Else

Else

171 (51.8)

163 (49.4)

Reference

Reference

US1

G

GG

9 (7.9)

3 (2.6)

3.1 (0.8, 12)

0.1014

 

G

Else

19 (16.7)

16 (13.9)

1.23 (0.58, 2.59)

0.5955

 

Else

GG

23 (20.2)

31 (27)

0.77 (0.4, 1.45)

0.4139

 

Else

Else

63 (55.3)

65 (56.5)

Reference

Reference

US2

G

AG

22 (5.7)

9 (2.4)

2.28 (1.03, 5.08)

0.0432

 

G

Else

108 (28.4)

123 (32.4)

0.82 (0.59, 1.13)

0.2279

 

Else

AG

40 (10.5)

52 (13.7)

0.72 (0.46, 1.13)

0.1306

 

Else

Else

210 (55.3)

196 (51.6)

Reference

Reference

(c)

Meta-analysis

  

OR (95% CI)

  

P-value

Interaction

  

2.46 (1.68, 3.70)

  

<0.00001

LPHN3 onlyb

  

1.04 (0.86, 1.25)

  

0.7111

Haplotype onlye

  

0.73 (0.61, 0.87)

  

<0.001

  1. Abbreviations: CI, confidence interval; OR, odds ratio; TDT, transmission disequilibrium test.
  2. aDemonstrates an OR of 4.47 (2.30–8.69) for having both susceptibility variants compared with the variant within LPHN3 itself.
  3. bDefined by the marker rs6551665 in chromosome 4.
  4. cDefined by the markers rs677642 and rs877137 in chromosome 11.
  5. dFor the Paisa sample the OR for the transmission of the susceptibility variants on 4q and 11q is 3.14 (95% CI=1.49–6.62) compared with transmission of neither variant, 2.15 (95% CI=0.9–5.1) compared with transmission solely of the susceptibility variant on 4q and 4.3 (95% CI=2.0–9.3) compared with the sole transmission of the susceptibility variant on 11q. For the German sample, the OR for the transmission of the susceptibility variants on 4q and 11q is 1.91 (95% CI=0.95–3.84) compared with transmission of neither variant, 1.72 (95% CI=0.80–3.71) compared with transmission solely of the susceptibility variant on 4q and 2.78 (95% CI=1.34–5.75) compared with the sole transmission of the susceptibility variant on 11q. For the USA1 sample, the OR for the transmission of the susceptibility variants followed the same trend as the other samples where on 4q and 11q, it is 3.10 (0.80–12) compared with transmission of neither variant, 2.53 (95% CI=0.58–10.95) compared with transmission solely of the susceptibility variant on 4q and 4.04 (95% CI=0.98–16.62) compared with the sole transmission of the susceptibility variant on 11q. For the USA2 sample, we see over-transmission of the susceptibility variants (P<0.04). The OR for variants on 4q and 11q is 2.28 (95% CI=1.03–5.08) compared with neither variant transmitted, 2.78 (95% CI=1.2–6.3) compared with transmission of only the susceptibility variant on 4q and 3.2 (95% CI=1.3–7.6) compared with transmission of only the susceptibility variant on 11q.
  6. eDefined by the markers rs677642 and rs877137 in chromosome 11 except in the US2 sample, for which it is defined by the markers rs754672 and rs965560.
  7. Note: TDT results after a combination of 4q–11q variants originates a definitive decrease of the original sample size, reported by Arcos-Burgos et al. (2010). The decrease of the sample size occurs as a consequence of the ad hoc strategy of conditioning on the fact of being a carrier of the G variant of susceptibility at rs6551665. Furthermore, because of genotype limitations, the Norwegian and Spaniard samples were not genotyped for markers in 11q, and given that TDT was selected to evaluate interaction effects, much information contained in the original family structure sample was lost.
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